Cathelicidins: Opportunities and Challenges in Skin Therapeutics and Clinical Translation
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články, přehledy
Grantová podpora
101090272
Horizon Europe
TQ03000264
Technology Agency of the Czech Republic
LX22NPO5102
Ministry of Education, Youth and Sports, Czech Republic
CZ.02.01.01/00/23_021/0008856
ERDF Programme Johannes Amos Comenius, Czech Republic
PubMed
39858288
PubMed Central
PMC11762488
DOI
10.3390/antibiotics14010001
PII: antibiotics14010001
Knihovny.cz E-zdroje
- Klíčová slova
- cathelicidins, clinical trials, peptide formulations, recombinant production, resistance mechanism, skin drug delivery, wound healing,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine.
Zobrazit více v PubMed
Antimicrobial Peptide Database. [(accessed on 16 December 2024)]. Available online: https://aps.unmc.edu/home.
Bhattacharjya S., Zhang Z., Ramamoorthy A. LL-37: Structures, antimicrobial activity, and influence on amyloid-related diseases. Biomolecules. 2024;14:320. doi: 10.3390/biom14030320. PubMed DOI PMC
Kościuczuk E.M., Lisowski P., Jarczak J., Strzałkowska N., Jóźwik A., Horbańczuk J., Krzyżewski J., Zwierzchowski L., Bagnicka E. Cathelicidins: Family of antimicrobial peptides. A review. Mol. Biol. Rep. 2012;39:10957–10970. doi: 10.1007/s11033-012-1997-x. PubMed DOI PMC
Alencar-Silva T., Braga M.C., Santana G.O.S., Saldanha-Araujo F., Pogue R., Dias S.C., Franco O.L., Carvalho J.L. Breaking the frontiers of cosmetology with antimicrobial peptides. Biotechnol. Adv. 2018;36:2019–2031. doi: 10.1016/j.biotechadv.2018.08.005. PubMed DOI
Dijksteel G.S., Ulrich M.M.W., Middelkoop E., Boekema B.K.H.L. Review: Lessons learned from clinical trials using antimicrobial peptides (AMPs) Front. Microbiol. 2021;12:61697. doi: 10.3389/fmicb.2021.616979. PubMed DOI PMC
Moretta A., Scieuzo C., Petrone A.M., Salvia R., Manniello M.D., Franco A., Lucchetti D., Vassallo A., Vogel H., Sgambato A., et al. Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields. Front. Cell. Infect. Microbiol. 2021;11:668632. doi: 10.3389/fcimb.2021.668632. PubMed DOI PMC
Aghazadeh H., Memariani H., Ranjbar R., Pooshang Bagheri K. The activity and action mechanism of novel short selective LL-37-derived anticancer peptides against clinical isolates of Escherichia coli. Chem. Biol. Drug Des. 2019;93:75–83. doi: 10.1111/cbdd.13381. PubMed DOI
Zanetti M., Gennaro R., Romeo D. Cathelicidins: A novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 1995;374:1–5. doi: 10.1016/0014-5793(95)01050-O. PubMed DOI
Scheenstra M.R., van Harten R.M., Veldhuizen E.J.A., Haagsman H.P., Coorens M. Cathelicidins modulate TLR-activation and inflammation. Front. Immunol. 2020;11:1137. doi: 10.3389/fimmu.2020.01137. PubMed DOI PMC
Leite M.L., Duque H.M., Rodrigues G.R., da Cunha N.B., Franco O.L. The LL-37 domain: A clue to cathelicidin immunomodulatory response? Peptides. 2023;165:171011. doi: 10.1016/j.peptides.2023.171011. PubMed DOI
Chen C., Brock R., Luh F., Chou P.J., Larrick J.W., Huang R.F., Huang T.H. The solution structure of the active domain of CAP18—A lipopolysaccharide binding protein from rabbit leukocytes. FEBS Lett. 1995;370:46–52. doi: 10.1016/0014-5793(95)00792-8. PubMed DOI
Wang G., Narayana J.L., Mishra B., Zhang Y., Wang F., Wang C., Zarena D., Lushnikova T., Wang X. Design of antimicrobial peptides: Progress made with human cathelicidin LL-37. Adv. Exp. Med. Biol. 2019;1117:215–240. doi: 10.1007/978-981-13-3588-4_12. PubMed DOI
Wang G. Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J. Biol. Chem. 2008;283:32637–32643. doi: 10.1074/jbc.M805533200. PubMed DOI
Wang G., Mishra B., Epand R.F., Epand R.M. High-quality 3D structures shine light on antibacterial, anti-biofilm and antiviral activities of human cathelicidin LL-37 and its fragments. Biochim. Biophys. Acta. 2014;1838:2160–2172. doi: 10.1016/j.bbamem.2014.01.016. PubMed DOI PMC
Wang G., Elliott M., Cogen A.L., Ezell E.L., Gallo R.L., Hancock R.E. Structure, dynamics, and antimicrobial and immune modulatory activities of human LL-23 and its single-residue variants mutated on the basis of homologous primate cathelicidins. Biochemistry. 2012;51:653–664. doi: 10.1021/bi2016266. PubMed DOI PMC
Xhindoli D., Pacor S., Benincasa M., Scocchi M., Gennaro R., Tossi A. The human cathelicidin LL-37—A pore-forming antibacterial peptide and host-cell modulator. Biochim. Biophys. Acta. 2016;1858:546–566. doi: 10.1016/j.bbamem.2015.11.003. PubMed DOI
Baumann A., Kiener M.S., Haigh B., Perreten V., Summerfield A. Differential ability of bovine antimicrobial cathelicidins to mediate nucleic acid sensing by epithelial cells. Front. Immunol. 2017;8:59. doi: 10.3389/fimmu.2017.00059. PubMed DOI PMC
Gudmundsson G.H., Agerberth B., Odeberg J., Bergman T., Olsson B., Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur. J. Biochem. 1996;238:325–332. doi: 10.1111/j.1432-1033.1996.0325z.x. PubMed DOI
Sørensen O.E., Gram L., Johnsen A.H., Andersson E., Bangsbøll S., Tjabringa G.S., Hiemstra P.S., Malm J., Egesten A., Borregaard N. Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: A novel mechanism of generating antimicrobial peptides in vagina. J. Biol. Chem. 2003;278:28540–28546. doi: 10.1074/jbc.M301608200. Erratum in J. Biol. Chem. 2006, 281, 12999. PubMed DOI
Yamasaki K., Schauber J., Coda A., Lin H., Dorschner R.A., Schechter N.M., Bonnart C., Descargues P., Hovnanian A., Gallo R.L. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J. 2006;20:2068–2080. doi: 10.1096/fj.06-6075com. PubMed DOI
Murakami M., Lopez-Garcia B., Braff M., Dorschner R.A., Gallo R.L. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J. Immunol. 2004;172:3070–3077. doi: 10.4049/jimmunol.172.5.3070. PubMed DOI
Murakami M., Kameda K., Tsumoto H., Tsuda T., Masuda K., Utsunomiya R., Mori H., Miura Y., Sayama K. TLN-58, an additional hCAP18 processing form, found in the lesion vesicle of palmoplantar pustulosis in the skin. J. Investig. Dermatol. 2017;137:322–331. doi: 10.1016/j.jid.2016.07.044. PubMed DOI
Zelezetsky I., Pontillo A., Puzzi L., Antcheva N., Segat L., Pacor S., Crovella S., Tossi A. Evolution of the primate cathelicidin. Correlation between structural variations and antimicrobial activity. J. Biol. Chem. 2006;281:19861–19871. doi: 10.1074/jbc.M511108200. PubMed DOI
Zhao C., Nguyen T., Boo L.M., Hong T., Espiritu C., Orlov D., Wang W., Waring A., Lehrer R.I. RL-37, an alpha-helical antimicrobial peptide of the rhesus monkey. Antimicrob. Agents Chemother. 2001;45:2695–2702. doi: 10.1128/AAC.45.10.2695-2702.2001. PubMed DOI PMC
Romeo D., Skerlavaj B., Bolognesi M., Gennaro R. Structure and bactericidal activity of an antibiotic dodecapeptide purified from bovine neutrophils. J. Biol. Chem. 1988;263:9573–9575. doi: 10.1016/S0021-9258(19)81553-3. PubMed DOI
Gennaro R., Skerlavaj B., Romeo D. Purification, composition, and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect. Immun. 1989;57:3142–3146. doi: 10.1128/iai.57.10.3142-3146.1989. PubMed DOI PMC
Skerlavaj B., Gennaro R., Bagella L., Merluzzi L., Risso A., Zanetti M. Biological characterization of two novel cathelicidin-derived peptides and identification of structural requirements for their antimicrobial and cell lytic activities. J. Biol. Chem. 1996;271:28375–28381. doi: 10.1074/jbc.271.45.28375. PubMed DOI
Scocchi M., Wang S., Zanetti M. Structural organization of the bovine cathelicidin gene family and identification of a novel member. FEBS Lett. 1997;417:311–315. doi: 10.1016/S0014-5793(97)01310-0. PubMed DOI
Selsted M.E., Novotny M.J., Morris W.L., Tang Y.Q., Smith W., Cullor J.S. Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J. Biol. Chem. 1992;267:4292–4295. doi: 10.1016/S0021-9258(18)42830-X. PubMed DOI
Anderson R.C., Yu P.L. Isolation and characterisation of proline/arginine-rich cathelicidin peptides from ovine neutrophils. Biochem. Biophys. Res. Commun. 2003;312:1139–1146. doi: 10.1016/j.bbrc.2003.11.045. Erratum in Biochem. Biophys. Res. Commun. 2004, 315, 246. PubMed DOI
Yang L., Hang B.L., Xu Y.Z., Wang L., Xia X.J., Dong M.M. Biological activity of a novel bovine-borne antimicrobial peptide BSN-37. Chin. J. Vet. Sci. 2018;38:2088–2093. (In Chinese)
Brahma B., Patra M.C., Karri S., Chopra M., Mishra P., De B.C., Kumar S., Mahaty S., Thakur K., Poluri K.M., et al. Diversity, antimicrobial action and structure-activity relationship of buffalo cathelicidins. PLoS ONE. 2015;10:e0144741. doi: 10.1371/journal.pone.0144741. PubMed DOI PMC
Scocchi M., Bontempo D., Boscolo S., Tomasinsig L., Giulotto E., Zanetti M. Novel cathelicidins in horse leukocytes. FEBS Lett. 1999;457:459–464. doi: 10.1016/S0014-5793(99)01097-2. PubMed DOI
Lu Z., Wang Y., Zhai L., Che Q., Wang H., Du S., Wang D., Feng F., Liu J., Lai R., et al. Novel cathelicidin-derived antimicrobial peptides from Equus asinus. FEBS J. 2010;277:2329–2339. doi: 10.1111/j.1742-4658.2010.07648.x. PubMed DOI
Lawyer C., Pai S., Watabe M., Borgia P., Mashimo T., Eagleton L., Watabe K. Antimicrobial activity of a 13 amino acid tryptophan-rich peptide derived from a putative porcine precursor protein of a novel family of antibacterial peptides. FEBS Lett. 1996;390:95–98. doi: 10.1016/0014-5793(96)00637-0. PubMed DOI
Tamamura H., Murakami T., Horiuchi S., Sugihara K., Otaka A., Takada W., Ibuka T., Waki M., Yamamoto N., Fuji N. Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity. Chem. Pharm. Bull. 1995;43:853–858. doi: 10.1248/cpb.43.853. PubMed DOI
Storici P., Zanetti M. A novel cDNA sequence encoding a pig leukocyte antimicrobial peptide with a cathelin-like pro-sequence. Biochem. Biophys. Res. Commun. 1993;196:1363–1368. doi: 10.1006/bbrc.1993.2403. PubMed DOI
Kokryakov V.N., Harwig S.S., Panyutich E.A., Shevchenko A.A., Aleshina G.M., Shamova O.V., Korneva H.A., Lehrer R.I. Protegrins: Leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett. 1993;327:231–236. doi: 10.1016/0014-5793(93)80175-T. PubMed DOI
Zhao C., Liu L., Lehrer R.I. Identification of a new member of the protegrin family by cDNA cloning. FEBS Lett. 1994;346:285–288. doi: 10.1016/0014-5793(94)00493-5. PubMed DOI
Zhao C., Ganz T., Lehrer R.I. The structure of porcine protegrin genes. FEBS Lett. 1995;368:197–202. doi: 10.1016/0014-5793(95)00633-K. PubMed DOI
Zanetti M., Storici P., Tossi A., Scocchi M., Gennaro R. Molecular cloning and chemical synthesis of a novel antibacterial peptide derived from pig myeloid cells. J. Biol. Chem. 1994;269:7855–7858. doi: 10.1016/S0021-9258(17)37128-4. PubMed DOI
Tossi A., Scocchi M., Zanetti M., Storici P., Gennaro R. PMAP-37, a novel antibacterial peptide from pig myeloid cells. cDNA cloning, chemical synthesis and activity. Eur. J. Biochem. 1995;228:941–946. doi: 10.1111/j.1432-1033.1995.tb20344.x. PubMed DOI
Agerberth B., Lee J.Y., Bergman T., Carlquist M., Boman H.G., Mutt V., Jörnvall H. Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur. J. Biochem. 1991;202:849–854. doi: 10.1111/j.1432-1033.1991.tb16442.x. PubMed DOI
Harwig S.S., Kokryakov V.N., Swiderek K.M., Aleshina G.M., Zhao C., Lehrer R.I. Prophenin-1, an exceptionally proline-rich antimicrobial peptide from porcine leukocytes. FEBS Lett. 1995;362:65–69. doi: 10.1016/0014-5793(95)00210-Z. PubMed DOI
Zhao C., Ganz T., Lehrer R.I. Structures of genes for two cathelin-associated antimicrobial peptides: Prophenin-2 and PR-39. FEBS Lett. 1995;376:130–134. doi: 10.1016/0014-5793(95)01237-3. PubMed DOI
Jeon H., Le M.T., Ahn B., Cho H.S., Le V.C.Q., Yum J., Hong K., Kim J.H., Song H., Park C. Copy number variation of PR-39 cathelicidin, and identification of PR-35, a natural variant of PR-39 with reduced mammalian cytotoxicity. Gene. 2019;692:88–93. doi: 10.1016/j.gene.2018.12.065. PubMed DOI
Bagella L., Scocchi M., Zanetti M. cDNA sequences of three sheep myeloid cathelicidins. FEBS Lett. 1995;376:225–228. doi: 10.1016/0014-5793(95)01285-3. PubMed DOI
Mahoney M.M., Lee A.Y., Brezinski-Caliguri D.J., Huttner K.M. Molecular analysis of the sheep cathelin family reveals a novel antimicrobial peptide. FEBS Lett. 1995;377:519–522. doi: 10.1016/0014-5793(95)01390-3. PubMed DOI
Travis S.M., Anderson N.N., Forsyth W.R., Espiritu C., Conway B.D., Greenberg E.P., McCray P.B., Jr., Lehrer R.I., Welsh M.J., Tack B.F. Bactericidal activity of mammalian cathelicidin-derived peptides. Infect. Immun. 2000;68:2748–2755. doi: 10.1128/IAI.68.5.2748-2755.2000. PubMed DOI PMC
Huttner K.M., Lambeth M.R., Burkin H.R., Burkin D.J., Broad T.E. Localization and genomic organization of sheep antimicrobial peptide genes. Gene. 1998;206:85–91. doi: 10.1016/S0378-1119(97)00569-6. PubMed DOI
Shamova O.V., Orlov D.S., Zharkova M.S., Balandin S.V., Yamschikova E.V., Knappe D., Hoffman R., Kokryakov V.N., Ovchinnikova T.V. Minibactenecins ChBac7.Nα and ChBac7.Nβ—Antimicrobial peptides from leukocytes of the goat Capra hircus. Acta Naturae. 2016;8:136–146. doi: 10.32607/20758251-2016-8-3-136-146. PubMed DOI PMC
Shamova O., Orlov D., Stegemann C., Czihal P., Hoffmann R., Brogden K., Kolodkin N., Sakuta G., Tossi A., Sahl H.G., et al. ChBac3.4: A novel proline-rich antimicrobial peptide from goat leukocytes. Int. J. Pept. Res. Ther. 2009;15:31–42. doi: 10.1007/s10989-008-9159-7. DOI
Shamova O., Brogden K.A., Zhao C., Nguyen T., Kokryakov V.N., Lehrer R.I. Purification and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes. Infect. Immun. 1999;67:4106–4111. doi: 10.1128/IAI.67.8.4106-4111.1999. PubMed DOI PMC
Panteleev P.V., Safronova V.N., Kruglikov R.N., Bolosov I.A., Bogdanov I.V., Ovchinnikova T.V. A novel proline-rich cathelicidin from the Alpaca vicugna pacos with potency to combat antibiotic-resistant bacteria: Mechanism of action and the functional role of the C-terminal region. Membranes. 2022;12:515. doi: 10.3390/membranes12050515. PubMed DOI PMC
Treffers C., Chen L., Anderson R.C., Yu P.L. Isolation and characterisation of antimicrobial peptides from deer neutrophils. Int. J. Antimicrob. Agents. 2005;26:165–169. doi: 10.1016/j.ijantimicag.2005.05.001. PubMed DOI
Yan X., Zhong J., Liu H., Liu C., Zhang K., Lai R. The cathelicidin-like peptide derived from panda genome is a potential antimicrobial peptide. Gene. 2012;492:368–374. doi: 10.1016/j.gene.2011.11.009. PubMed DOI
Sang Y., Ortega M.T., Rune K., Xiau W., Zhang G., Soulages J.L., Lushington G.H., Fang J., Williams T.D., Blecha F., et al. Canine cathelicidin (K9CATH): Gene cloning, expression, and biochemical activity of a novel pro-myeloid antimicrobial peptide. Dev. Comp. Immunol. 2007;31:1278–1296. doi: 10.1016/j.dci.2007.03.007. PubMed DOI
Peel E., Cheng Y., Djordjevic J.T., Fox S., Sorrell T.C., Belov K. Cathelicidins in the tasmanian devil (Sarcophilus harrisii) Sci. Rep. 2016;6:35019. doi: 10.1038/srep35019. PubMed DOI PMC
Leonard B.C., Chu H., Johns J.L., Gallo R.L., Moore P.F., Marks S.L., Bevins C.L. Expression and activity of a novel cathelicidin from domestic cats. PLoS ONE. 2011;6:e18756. doi: 10.1371/journal.pone.0018756. PubMed DOI PMC
Wang J., Wong E.S., Whitley J.C., Li J., Stringer J.M., Short K.R., Renfree M.B., Belov K., Cocks B.G. Ancient antimicrobial peptides kill antibiotic-resistant pathogens: Australian mammals provide new options. PLoS ONE. 2011;6:e24030. doi: 10.1371/journal.pone.0024030. PubMed DOI PMC
Peel E., Cheng Y., Djordjevic J.T., Kuhn M., Sorrell T., Belov K. Marsupial and monotreme cathelicidins display antimicrobial activity, including against methicillin-resistant Staphylococcus aureus. Microbiology. 2017;163:1457–1465. doi: 10.1099/mic.0.000536. PubMed DOI
Cho H.S., Yum J., Larivière A., Lévêque N., Le Q.V.C., Ahn B., Jeon H., Hong K., Soundrarajan N., Kim J.H., et al. Opossum cathelicidins exhibit antimicrobial activity against a broad spectrum of pathogens including west Nile virus. Front. Immunol. 2020;11:347. doi: 10.3389/fimmu.2020.00347. PubMed DOI PMC
Peel E., Cheng Y., Djordjevic J.T., O’Meally D., Thomas M., Kuhn M., Sorrell T.C., Huston W.M., Belov K. Koala cathelicidin PhciCath5 has antimicrobial activity, including against Chlamydia pecorum. PLoS ONE. 2021;16:e0249658. doi: 10.1371/journal.pone.0249658. PubMed DOI PMC
Choi M., Cho H.S., Ahn B., Prathap S., Nagasundarapandian S., Park C. Genomewide analysis and biological characterization of cathelicidins with potent antimicrobial activity and low cytotoxicity from three bat species. Antibiotics. 2022;11:989. doi: 10.3390/antibiotics11080989. PubMed DOI PMC
Otazo-Pérez A., Asensio-Calavia P., González-Acosta S., Baca-González V., López M.R., Morales-delaNuez A., Pérez de la Lastra J.M. Antimicrobial activity of cathelicidin-derived peptide from the iberian mole Talpa occidentalis. Vaccines. 2022;10:1105. doi: 10.3390/vaccines10071105. PubMed DOI PMC
Cho H.S., Soundrarajan N., Le Van Chanh Q., Jeon H., Cha S.Y., Kang M., Ahn B.Y., Hong K., Song H., Kim J.H., et al. The novel cathelicidin of naked mole rats, Hg-CATH, showed potent antimicrobial activity and low cytotoxicity. Gene. 2018;676:164–170. doi: 10.1016/j.gene.2018.07.005. PubMed DOI
Pestonjamasp V.K., Huttner K.H., Gallo R.L. Processing site and gene structure for the murine antimicrobial peptide CRAMP. Peptides. 2001;22:1643–1650. doi: 10.1016/S0196-9781(01)00499-5. PubMed DOI
Larrick J.W., Hirata M., Shimomoura Y., Yoshida M., Zheng H., Zhong J., Wright S.C. Antimicrobial activity of rabbit CAP18-derived peptides. Antimicrob. Agents Chemother. 1993;37:2534–2539. doi: 10.1128/AAC.37.12.2534. PubMed DOI PMC
Li C., Cai Y., Luo L., Tian G., Wang X., Yan A., Wang L., Wu S., Wu Z., Zhang T., et al. TC-14, a cathelicidin-derived antimicrobial peptide with broad-spectrum antibacterial activity and high safety profile. iScience. 2024;27:110404. doi: 10.1016/j.isci.2024.110404. PubMed DOI PMC
Yomogida S., Nagaoka I., Yamashita T. Comparative studies on the extracellular release and biological activity of guinea pig neutrophil cationic antibacterial polypeptide of 11 kDa (CAP11) and defensins. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 1997;116:99–107. doi: 10.1016/S0305-0491(96)00222-2. PubMed DOI
Wang J., Zhang M., Li C., Liu M., Qi Y., Xie X., Zhou C., Ma L. A novel cathelicidin TS-CATH derived from Thamnophis sirtalis combats drug-resistant gram-negative bacteria in vitro and in vivo. Comput. Struct. Biotechnol. J. 2024;23:2388–2406. doi: 10.1016/j.csbj.2024.05.020. PubMed DOI PMC
Xiao Y., Cai Y., Bommineni Y.R., Fernando S.C., Prakash O., Gilliland S.E., Zhang G. Identification and functional characterization of three chicken cathelicidins with potent antimicrobial activity. J. Biol. Chem. 2006;281:2858–2867. doi: 10.1074/jbc.M507180200. PubMed DOI
van Dijk A., Veldhuizen E.J., van Asten A.J., Haagsman H.P. CMAP27, a novel chicken cathelicidin-like antimicrobial protein. Vet. Immunol. Immunopathol. 2005;106:321–327. doi: 10.1016/j.vetimm.2005.03.003. PubMed DOI
Goitsuka R., Chen C.L., Benyon L., Asano Y., Kitamura D., Cooper M.D. Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway. Proc. Natl. Acad. Sci. USA. 2007;104:15063–15068. doi: 10.1073/pnas.0707037104. PubMed DOI PMC
Yu H., Lu Y., Qiao X., Wei L., Fu T., Cai S., Wang C., Liu X., Zhong S., Wang Y. Novel cathelicidins from pigeon highlights evolutionary convergence in avain cathelicidins and functions in modulation of innate immunity. Sci. Rep. 2015;5:11082. doi: 10.1038/srep11082. PubMed DOI PMC
Gao W., Xing L., Qu P., Tan T., Yang N., Li D., Chen H., Feng X. Identification of a novel cathelicidin antimicrobial peptide from ducks and determination of its functional activity and antibacterial mechanism. Sci. Rep. 2015;5:17260. doi: 10.1038/srep17260. PubMed DOI PMC
Wang Y., Lu Z., Feng F., Zhu W., Guang H., Liu J., He W., Chi L., Li W., Yu H. Molecular cloning and characterization of novel cathelicidin-derived myeloid antimicrobial peptide from Phasianus colchicus. Dev. Comp. Immunol. 2011;35:314–322. doi: 10.1016/j.dci.2010.10.004. PubMed DOI
Feng F., Chen C., Zhu W., He W., Guang H., Li Z., Wang D., Liu J., Chen M., Wang Y., et al. Gene cloning, expression and characterization of avian cathelicidin orthologs, Cc-CATHs, from Coturnix coturnix. FEBS J. 2011;278:1573–1584. doi: 10.1111/j.1742-4658.2011.08080.x. PubMed DOI
Kannoth S., Ali N., Prasanth G.K., Arvind K., Mohany M., Hembrom P.S., Sadanandan S., Vasu D.A., Grace T. Transcriptome analysis of Corvus splendens reveals a repertoire of antimicrobial peptides. Sci. Rep. 2023;13:18728. doi: 10.1038/s41598-023-45875-w. PubMed DOI PMC
Broekman D.C., Frei D.M., Gylfason G.A., Steinarsson A., Jörnvall H., Agerberth B., Gudmundsson G.H., Maier V.H. Cod cathelicidin: Isolation of the mature peptide, cleavage site characterisation and developmental expression. Dev. Comp. Immunol. 2011;35:296–303. doi: 10.1016/j.dci.2010.10.002. PubMed DOI
Lu X.J., Chen J., Huang Z.A., Shi Y.H., Lu J.N. Identification and characterization of a novel cathelicidin from ayu, Plecoglossus altivelis. Fish Shellfish Immunol. 2011;31:52–57. doi: 10.1016/j.fsi.2011.03.005. PubMed DOI
Li Z., Zhang S., Gao J., Guang H., Tian Y., Zhao Z., Wang Y., Yu H. Structural and functional characterization of CATH_BRALE, the defense molecule in the ancient salmonoid, Brachymystax lenok. Fish Shellfish Immunol. 2013;34:1–7. doi: 10.1016/j.fsi.2012.07.004. PubMed DOI
Uzzell T., Stolzenberg E.D., Shinnar A.E., Zasloff M. Hagfish intestinal antimicrobial peptides are ancient cathelicidins. Peptides. 2003;24:1655–1667. doi: 10.1016/j.peptides.2003.08.024. PubMed DOI
Chang C.I., Pleguezuelos O., Zhang Y.A., Zou J., Secombes C.J. Identification of a novel cathelicidin gene in the rainbow trout, Oncorhynchus mykiss. Infect. Immun. 2005;73:5053–5064. doi: 10.1128/IAI.73.8.5053-5064.2005. PubMed DOI PMC
Zhang X.J., Zhang X.Y., Zhang N., Guo X., Peng K.S., Wu H., Lu L.F., Wu N., Chen D.D., Li S., et al. Distinctive structural hallmarks and biological activities of the multiple cathelicidin antimicrobial peptides in a primitive teleost fish. J. Immunol. 2015;194:4974–4987. doi: 10.4049/jimmunol.1500182. PubMed DOI
Zhao H., Gan T.X., Liu X.D., Jin Y., Lee W.H., Shen J.H., Zhang Y. Identification and characterization of novel reptile cathelicidins from elapid snakes. Peptides. 2008;29:1685–1691. doi: 10.1016/j.peptides.2008.06.008. PubMed DOI
Wei L., Gao J., Zhang S., Wu S., Xie Z., Ling G., Kuang Y.Q., Yang Y., Yu H., Wang Y. Identification and characterization of the first cathelicidin from sea snakes with potent antimicrobial and anti-inflammatory activity and special mechanism. J. Biol. Chem. 2015;290:16633–16652. doi: 10.1074/jbc.M115.642645. PubMed DOI PMC
Falcao C.B., de La Torre B.G., Pérez-Peinado C., Barron A.E., Andreu D., Rádis-Baptista G. Vipericidins: A novel family of cathelicidin-related peptides from the venom gland of South American pit vipers. Amino Acids. 2014;46:2561–2571. doi: 10.1007/s00726-014-1801-4. PubMed DOI
Wang Y., Hong J., Liu X., Yang H., Liu R., Wu J., Wang A., Lin D., Lai R. Snake cathelicidin from Bungarus fasciatus is a potent peptide antibiotics. PLoS ONE. 2008;3:e3217. doi: 10.1371/journal.pone.0003217. PubMed DOI PMC
Cai S., Qiao X., Feng L., Shi N., Wang H., Yang H., Guo Z., Wang M., Chen Y., Wang Y., et al. Python cathelicidin CATHPb1 protects against multidrug-resistant staphylococcal infections by antimicrobial-immunomodulatory duality. J. Med. Chem. 2018;61:2075–2086. doi: 10.1021/acs.jmedchem.8b00036. PubMed DOI
Wang A., Zhang F., Guo Z., Chen Y., Zhang M., Yu H., Wang Y. Characterization of a cathelicidin from the colubrinae snake, Sinonatrix annularis. Zool. Sci. 2019;36:68–76. doi: 10.2108/zs180064. PubMed DOI
Hernández-Arvizu E.E., Silis-Moreno T.M., García-Arredondo J.A., Rodríguez-Torres A., Cervantes-Chávez J.A., Mosqueda J. Aquiluscidin, a cathelicidin from Crotalus aquilus, and the Vcn-23 derivative peptide, have anti-microbial activity against gram-negative and gram-positive bacteria. Microorganisms. 2023;11:2778. doi: 10.3390/microorganisms11112778. PubMed DOI PMC
Cai Y., Wang X., Zhang T., Yan A., Luo L., Li C., Tian G., Wu Z., Wang X., Shen D., et al. Rational design of a potent antimicrobial peptide based on the active region of a gecko cathelicidin. ACS Infect. Dis. 2024;10:951–960. doi: 10.1021/acsinfecdis.3c00575. PubMed DOI
Cai S., Meng K., Liu P., Cao X., Wang G. Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans. Arch. Oral Biol. 2021;129:105205. doi: 10.1016/j.archoralbio.2021.105205. PubMed DOI
Shi N., Cai S., Gao J., Qiao X., Yang H., Wang Y., Yu H. Roles of polymorphic cathelicidins in innate immunity of soft-shell turtle, Pelodiscus sinensis. Dev. Comp. Immunol. 2019;92:179–192. doi: 10.1016/j.dci.2018.11.010. PubMed DOI
Qiao X., Yang H., Gao J., Zhang F., Chu P., Yang Y., Zhang M., Wang Y., Yu H. Diversity, immunoregulatory action and structure-activity relationship of green sea turtle cathelicidins. Dev. Comp. Immunol. 2019;98:189–204. doi: 10.1016/j.dci.2019.05.005. PubMed DOI
Chen Y., Cai S., Qiao X., Wu M., Guo Z., Wang R., Kuang Y.Q., Yu H., Wang Y. As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses. Biochem. J. 2017;474:2861–2885. doi: 10.1042/BCJ20170334. PubMed DOI
Santana F.L., Estrada K., Alford M.A., Wu B.C., Dostert M., Pedraz L., Akhoundsadegh N., Kalsi P., Haney E.F., Straus S.K., et al. Novel alligator cathelicidin As-CATH8 demonstrates anti-infective activity against clinically relevant and crocodylian bacterial pathogens. Antibiotics. 2022;11:1603. doi: 10.3390/antibiotics11111603. PubMed DOI PMC
Barksdale S.M., Hrifko E.J., van Hoek M.L. Cathelicidin antimicrobial peptide from Alligator mississippiensis has antibacterial activity against multi-drug resistant Acinetobacter baumanii and Klebsiella pneumoniae. Dev. Comp. Immunol. 2017;70:135–144. doi: 10.1016/j.dci.2017.01.011. PubMed DOI
Hao X., Yang H., Wei L., Yang S., Zhu W., Ma D., Yu H., Lai R. Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate. Amino Acids. 2012;43:677–685. doi: 10.1007/s00726-011-1116-7. PubMed DOI
Wei L., Yang J., He X., Mo G., Hong J., Yan X., Lin D., Lai R. Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide. J. Med. Chem. 2013;56:3546–3556. doi: 10.1021/jm4004158. PubMed DOI
Yu H., Cai S., Gao J., Zhang S., Lu Y., Qiao X., Yang H., Wang Y. Identification and polymorphism discovery of the cathelicidins, Lf-CATHs in ranid amphibian (Limnonectes fragilis) FEBS J. 2013;280:6022–6032. doi: 10.1111/febs.12521. PubMed DOI
Ling G., Gao J., Zhang S., Xie Z., Wei L., Yu H., Wang Y. Cathelicidins from the bullfrog Rana catesbeiana provides novel template for peptide antibiotic design. PLoS ONE. 2014;9:e93216. doi: 10.1371/journal.pone.0093216. PubMed DOI PMC
Sun T., Zhan B., Gao Y. A novel cathelicidin from Bufo bufo gargarizans Cantor showed specific activity to its habitat bacteria. Gene. 2015;571:172–177. doi: 10.1016/j.gene.2015.06.034. PubMed DOI
Mu L., Zhou L., Yang J., Zhuang L., Tang J., Liu T., Wu J., Yang H. The first identified cathelicidin from tree frogs possesses anti-inflammatory and partial LPS neutralization activities. Amino Acids. 2017;49:1571–1585. doi: 10.1007/s00726-017-2449-7. PubMed DOI PMC
Qi R.H., Chen Y., Guo Z.L., Zhang F., Fang Z., Huang K., Yu H.N., Wang X.P. Identification and characterization of two novel cathelicidins from the frog Odorrana livida. Zool. Res. 2019;40:94–101. doi: 10.24272/j.issn.2095-8137.2018.062. PubMed DOI PMC
Chen J., Lin Y.F., Chen J.H., Chen X., Lin Z.H. Molecular characterization of cathelicidin in tiger frog (Hoplobatrachus rugulosus): Antimicrobial activity and immunomodulatory activity. Comp. Biochem. Physiol. Part C Toxicol. Pharmacol. 2021;247:109072. doi: 10.1016/j.cbpc.2021.109072. PubMed DOI
Chai J., Chen X., Ye T., Zeng B., Zeng Q., Wu J., Kascakova B., Martins L.A., Prudnikova T., Smatanova I.K., et al. Characterization and functional analysis of cathelicidin-MH, a novel frog-derived peptide with anti-septicemic properties. eLife. 2021;10:e64411. doi: 10.7554/eLife.64411. PubMed DOI PMC
Wang Y., Ouyang J., Luo X., Zhang M., Jiang Y., Zhang F., Zhou J., Wang Y. Identification and characterization of novel bi-functional cathelicidins from the black-spotted frog (Pelophylax nigromaculata) with both anti-infective and antioxidant activities. Dev. Comp. Immunol. 2021;116:103928. doi: 10.1016/j.dci.2020.103928. PubMed DOI
Luo Q., Deng H., Yin M., Chen C., Zhou J. Novel cathelicidin antimicrobial peptides from Paa robertingeri. Ann. Res. Rev. Biol. 2019;32:1–10. doi: 10.9734/arrb/2019/v32i430093. DOI
Chen J., Zhang C.Y., Wang Y., Zhang L., Seah R.W.X., Ma L., Ding G.H. Discovery of Ll-CATH: A novel cathelicidin from the Chong’an Moustache Toad (Leptobrachium liui) with antibacterial and immunomodulatory activity. BMC Vet. Res. 2024;20:343. doi: 10.1186/s12917-024-04202-9. PubMed DOI PMC
Zheng W.C., Cheng X.Y., Tao Y.H., Mao Y.S., Lu C.P., Lin Z.H., Chen J. Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa) Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2024;283:109943. doi: 10.1016/j.cbpc.2024.109943. PubMed DOI
Wu J., Yang J., Wang X., Wei L., Mi K., Shen Y., Liu T., Yang H., Mu L. A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice. Biochem. J. 2018;475:2785–2799. doi: 10.1042/BCJ20180286. PubMed DOI PMC
Shi J., Wu J., Chen Q., Shen Y., Mi K., Yang H., Mu L. A frog-derived cathelicidin peptide with dual antimicrobial and immunomodulatory activities effectively ameliorates Staphylococcus aureus-induced peritonitis in mice. ACS Infect. Dis. 2022;8:2464–2479. doi: 10.1021/acsinfecdis.2c00260. PubMed DOI
He Y., Shen Y., Feng X., Ruan S., Zhao Y., Mu L., Wu J., Yang H. Tree frog-derived cathelicidin protects mice against bacterial infection through its antimicrobial and anti-inflammatory activities and regulatory effect on phagocytes. ACS Infect. Dis. 2023;9:2252–2268. doi: 10.1021/acsinfecdis.3c00316. PubMed DOI
Shi Y., Li C., Wang M., Chen Z., Luo Y., Xia X.S., Song Y., Sun Y., Zhang A.M. Cathelicidin-DM is an antimicrobial peptide from Duttaphrynus melanostictus and has wound-healing therapeutic potential. ACS Omega. 2020;5:9301–9310. doi: 10.1021/acsomega.0c00189. PubMed DOI PMC
Gao F., Xu W.F., Tang L.P., Wang M.M., Wang X.J., Qian Y.C. Characteristics of cathelicidin-Bg, a novel gene expressed in the ear-side gland of Bufo gargarizans. Genet. Mol. Res. 2016;15:gmr.15038481. doi: 10.4238/gmr.15038481. PubMed DOI
Yang H., Lu B., Zhou D., Zhao L., Song W., Wang L. Identification of the first cathelicidin gene from skin of chinese giant salamanders Andrias davidianus with its potent antimicrobial activity. Dev. Comp. Immunol. 2017;77:141–149. doi: 10.1016/j.dci.2017.08.002. PubMed DOI
Eissa A., Amodeo V., Smith C.R., Diamandis E.P. Kallikrein-related peptidase-8 (KLK8) is an active serine protease in human epidermis and sweat and is involved in a skin barrier proteolytic cascade. J. Biol. Chem. 2011;286:687–706. doi: 10.1074/jbc.M110.125310. PubMed DOI PMC
Sørensen O.E., Follin P., Johnsen A.H., Calafat J., Tjabringa G.S., Hiemstra P.S., Borregaard N. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood. 2001;97:3951–3959. doi: 10.1182/blood.V97.12.3951. PubMed DOI
Matus C.E., Ehrenfeld P., Figueroa C.D. The family of kallikrein-related peptidases and kinin peptides as modulators of epidermal homeostasis. Am. J. Physiol. Cell Physiol. 2022;323:C1070–C1087. doi: 10.1152/ajpcell.00012.2022. PubMed DOI
Niyonsaba F., Kiatsurayanon C., Chieosilapatham P., Ogawa H. Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases. Exp. Dermatol. 2017;26:989–998. doi: 10.1111/exd.13314. PubMed DOI
Suwanchote S., Waitayangkoon P., Chancheewa B., Inthanachai T., Niwetbowornchai N., Edwards S.W., Virakul S., Thammahong A., Kiatsurayanon C., Rerknimitr P., et al. Role of antimicrobial peptides in atopic dermatitis. Int. J. Dermatol. 2022;61:532–540. doi: 10.1111/ijd.15814. PubMed DOI
Zhang Q.Y., Yan Z.B., Meng Y.M., Hong X.Y., Shao G., Ma J.J., Cheng X.R., Liu J., Kang J., Fu C.Y. Antimicrobial peptides: Mechanism of action, activity and clinical potential. Mil. Med. Res. 2021;8:48. doi: 10.1186/s40779-021-00343-2. PubMed DOI PMC
Lin T.Y., Weibel D.B. Organization and function of anionic phospholipids in bacteria. Appl. Microbiol. Biotechnol. 2016;100:4255–4267. doi: 10.1007/s00253-016-7468-x. PubMed DOI
Renne M.F., de Kroon A.I.P.M. The role of phospholipid molecular species in determining the physical properties of yeast membranes. FEBS Lett. 2018;592:1330–1345. doi: 10.1002/1873-3468.12944. PubMed DOI PMC
Huan Y., Kong Q., Mou H., Yi H. Antimicrobial peptides: Classification, design, application and research progress in multiple fields. Front. Microbiol. 2020;11:582779. doi: 10.3389/fmicb.2020.582779. PubMed DOI PMC
Li X., Zuo S., Wang B., Zhang K., Wang Y. Antimicrobial mechanisms and clinical application prospects of antimicrobial peptides. Molecules. 2022;27:2675. doi: 10.3390/molecules27092675. PubMed DOI PMC
Langham A.A., Ahmad A.S., Kaznessis Y.N. On the nature of antimicrobial activity: A model for protegrin-1 pores. J. Am. Chem. Soc. 2008;130:4338–4346. doi: 10.1021/ja0780380. PubMed DOI PMC
Bolintineanu D.S., Vivcharuk V., Kaznessis Y.N. Multiscale models of the antimicrobial peptide protegrin-1 on gram-negative bacteria membranes. Int. J. Mol. Sci. 2012;13:11000–11011. doi: 10.3390/ijms130911000. PubMed DOI PMC
Lipkin R.B., Lazaridis T. Implicit membrane investigation of the stability of antimicrobial peptide β-barrels and arcs. J. Membr. Biol. 2015;248:469–486. doi: 10.1007/s00232-014-9759-4. PubMed DOI PMC
Hale J.D., Hancock R.E. Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev. Anti-Infect. Ther. 2007;5:951–959. doi: 10.1586/14787210.5.6.951. PubMed DOI
Mookherjee N., Anderson M.A., Haagsman H.P., Davidson D.J. Antimicrobial host defense peptides: Functions and clinical potential. Nat. Rev. Drug Discov. 2020;19:311–332. doi: 10.1038/s41573-019-0058-8. PubMed DOI
Majewska M., Zamlynny V., Pieta I.S., Nowakowski R., Pieta P. Interaction of LL-37 human cathelicidin peptide with a model microbial-like lipid membrane. Bioelectrochemistry. 2021;141:107842. doi: 10.1016/j.bioelechem.2021.107842. PubMed DOI
Shenkarev Z.O., Balandin S.V., Trunov K.I., Paramonov A.S., Sukhanov S.V., Barsukov L.I., Arseniev A.S., Ovchinnikova T.V. Molecular mechanism of action of β-hairpin antimicrobial peptide arenicin: Oligomeric structure in dodecylphosphocholine micelles and pore formation in planar lipid bilayers. Biochemistry. 2011;50:6255–6265. doi: 10.1021/bi200746t. PubMed DOI
Corrêa J.A.F., Evangelista A.G., Nazareth T.D.M., Luciano F.B. Fundamentals on the molecular mechanism of action of antimicrobial peptides. Materialia. 2019;8:100494. doi: 10.1016/j.mtla.2019.100494. DOI
Cardoso M.H., Meneguetti B.T., Costa B.O., Buccini D.F., Oshiro K.G.N., Preza S.L.E., Carvalho C.M.E., Migliolo L., Franco O.L. Non-lytic antibacterial peptides that translocate through bacterial membranes to act on intracellular targets. Int. J. Mol. Sci. 2019;20:4877. doi: 10.3390/ijms20194877. PubMed DOI PMC
Mardirossian M., Barrière Q., Timchenko T., Müller C., Pacor S., Mergaert P., Scocchi M., Wilson D.N. Fragments of the nonlytic proline-rich antimicrobial peptide Bac5 kill Escherichia coli cells by inhibiting protein synthesis. Antimicrob. Agents Chemother. 2018;62:e00534-18. doi: 10.1128/AAC.00534-18. PubMed DOI PMC
Yang H., Fu J., Zhao Y., Shi H., Hu H., Wang H. Escherichia coli PagP enzyme-based de novo design and in vitro activity of antibacterial peptide LL-37. Med. Sci. Monit. 2017;23:2558–2564. doi: 10.12659/MSM.902095. PubMed DOI PMC
Tripathi S., Verma A., Kim E.J., White M.R., Hartshorn K.L. LL-37 modulates human neutrophil responses to influenza A virus. J. Leukoc. Biol. 2014;96:931–938. doi: 10.1189/jlb.4A1113-604RR. PubMed DOI PMC
Brice D.C., Toth Z., Diamond G. LL-37 disrupts the Kaposi’s sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells. Antivir. Res. 2018;158:25–33. doi: 10.1016/j.antiviral.2018.07.025. PubMed DOI PMC
Sousa F.H., Casanova V., Findlay F., Stevens C., Svoboda P., Pohl J., Proudfoot L., Barlow P.G. Cathelicidins display conserved direct antiviral activity towards rhinovirus. Peptides. 2017;95:76–83. doi: 10.1016/j.peptides.2017.07.013. PubMed DOI PMC
Ordonez S.R., Amarullah I.H., Wubbolts R.W., Veldhuizen E.J., Haagsman H.P. Fungicidal mechanisms of cathelicidins LL-37 and CATH-2 revealed by live-cell imaging. Antimicrob. Agents Chemother. 2014;58:2240–2248. doi: 10.1128/AAC.01670-13. PubMed DOI PMC
Choi K.Y., Mookherjee N. Multiple immune-modulatory functions of cathelicidin host defense peptides. Front. Immunol. 2012;3:149. doi: 10.3389/fimmu.2012.00149. PubMed DOI PMC
Agier J., Efenberger M., Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Cent. Eur. J. Immunol. 2015;40:225–235. doi: 10.5114/ceji.2015.51359. PubMed DOI PMC
Hancock R.E., Haney E.F., Gill E.E. The immunology of host defense peptides: Beyond antimicrobial activity. Nat. Rev. Immunol. 2016;16:321–334. doi: 10.1038/nri.2016.29. PubMed DOI
Mookherjee N., Lippert D.N., Hamill P., Falsafi R., Nijnik A., Kindrachuk J., Pistolic J., Gardy J., Miri P., Naseer M., et al. Intracellular receptor for human host defense peptide LL-37 in monocytes. J. Immunol. 2009;183:2688–2696. doi: 10.4049/jimmunol.0802586. PubMed DOI
Zhang Z., Cherryholmes G., Chang F., Rose D.M., Schraufstatter I., Shively J.E. Evidence that cathelicidin peptide LL-37 may act as a functional ligand for CXCR2 on human neutrophils. Eur. J. Immunol. 2009;39:3181–3194. doi: 10.1002/eji.200939496. PubMed DOI PMC
Zheng Y., Niyonsaba F., Ushio H., Nagaoka I., Ikeda S., Okumura K., Ogawa H. Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br. J. Dermatol. 2007;157:1124–1131. doi: 10.1111/j.1365-2133.2007.08196.x. PubMed DOI
Beaumont P.E., McHugh B., Findlay E.G., Mackellar A., Mackenzie K.J., Gallo R.L., Govan J.R.W., Simpson A.J., Davidson D.J. Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo. PLoS ONE. 2014;9:e99029. doi: 10.1371/journal.pone.0099029. PubMed DOI PMC
Davidson D.J., Currie A.J., Reid G.S., Bowdish D.M., MacDonald K.L., Ma R.C., Hancock R.E.W., Speert D.P. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol. 2004;172:1146–1156. doi: 10.4049/jimmunol.172.2.1146. PubMed DOI
Findlay E.G., Currie A.J., Zhang A., Ovciarikova J., Young L., Stevens H., McHugh B.J., Canel M., Gray M., Milling S.W.F., et al. Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy. Oncoimmunology. 2019;8:1608106. doi: 10.1080/2162402X.2019.1608106. PubMed DOI PMC
Kim S.H., Kim Y.N., Jang Y.S. Cutting edge: LL-37-mediated formyl peptide receptor-2 signaling in follicular dendritic cells contributes to B cell activation in Peyer’s patch germinal centers. J. Immunol. 2017;198:629–633. doi: 10.4049/jimmunol.1600886. PubMed DOI
Putsep K., Carlsson G., Boman H.G., Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: An observation study. Lancet. 2002;360:1144–1149. doi: 10.1016/S0140-6736(02)11201-3. PubMed DOI
Severino P., Ariga S.K., Barbeiro H.V., de Lima T.M., de Paula Silva E., Barbeiro D.F., Machado M.C.C., Nizet V., da Silva F.P. Cathelicidin-deficient mice exhibit increased survival and upregulation of key inflammatory response genes following cecal ligation and puncture. J. Mol. Med. 2017;95:995–1003. doi: 10.1007/s00109-017-1555-z. PubMed DOI
Niyonsaba F., Suzuki A., Ushio H., Nagaoka I., Ogawa H., Okumura K. The human antimicrobial peptide dermcidin activates normal human keratinocytes. Br. J. Dermatol. 2009;160:243–249. doi: 10.1111/j.1365-2133.2008.08925.x. PubMed DOI
Kahlenberg J.M., Kaplan M.J. Little peptide, big effects: The role of LL-37 in inflammation and autoimmune disease. J. Immunol. 2013;191:4895–4901. doi: 10.4049/jimmunol.1302005. PubMed DOI PMC
Dombrowski Y., Peric M., Koglin S., Kammerbauer C., Göss C., Anz D., Simanski M., Gläser R., Harder J., Hornung V., et al. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl. Med. 2011;3:82ra38. doi: 10.1126/scitranslmed.3002001. PubMed DOI PMC
Chen X., Niyonsaba F., Ushio H., Nagaoka I., Ikeda S., Okumura K., Ogawa H. Human cathelicidin LL-37 increases vascular permeability in the skin via mast cell activation, and phosphorylates MAP kinases p38 and ERK in mast cells. J. Dermatol. Sci. 2006;43:63–66. doi: 10.1016/j.jdermsci.2006.03.001. PubMed DOI
Niyonsaba F., Ushio H., Hara M., Yokoi H., Tominaga M., Takamori K., Kajiwara N., Saito H., Nagaoka I., Ogawa H., et al. Antimicrobial peptides human beta-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. J. Immunol. 2010;184:3526–3534. doi: 10.4049/jimmunol.0900712. PubMed DOI
Ganguly D., Chamilos G., Lande R., Gregorio J., Meller S., Facchinetti V., Homey B., Barrat F.J., Zal T., Gilliet M. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 2009;206:1983–1994. doi: 10.1084/jem.20090480. PubMed DOI PMC
Morizane S., Yamasaki K., Mühleisen B., Kotol P.F., Murakami M., Aoyama Y., Iwatsuki K., Hata T., Gallo R.L. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J. Investig. Dermatol. 2012;132:135–143. doi: 10.1038/jid.2011.259. PubMed DOI PMC
Smithrithee R., Niyonsaba F., Kiatsurayanon C., Ushio H., Ikeda S., Okumura K., Ogawa H. Human β-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes. J. Dermatol. Sci. 2015;77:46–53. doi: 10.1016/j.jdermsci.2014.12.001. PubMed DOI
Yamasaki K., Di Nardo A., Bardan A., Murakami M., Ohtake T., Coda A., Dorschner R.A., Bonnart C., Descargues P., Hovnanian A., et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat. Med. 2007;13:975–980. doi: 10.1038/nm1616. PubMed DOI
Yamasaki K., Kanada K., Macleod D.T., Borkowski A.W., Morizane S., Nakatsuji T., Cogen A.L., Gallo R.L. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J. Investig. Dermatol. 2011;131:688–697. doi: 10.1038/jid.2010.351. PubMed DOI PMC
Diegelmann R.F., Evans M.C. Wound healing: An overview of acute, fibrotic and delayed healing. Front. Biosci. 2004;9:283–289. doi: 10.2741/1184. PubMed DOI
Park H.J., Cho D.H., Kim H.J. Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37. J. Investig. Dermatol. 2009;129:843–850. doi: 10.1038/jid.2008.320. PubMed DOI PMC
Ramos R., Silva J.P., Rodrigues A.C., Costa R., Guardão L., Schmitt F., Raquel Soares R., Vilanova M., Domingues L., Gama M. Wound healing activity of the human antimicrobial peptide LL37. Peptides. 2011;32:1469–1476. doi: 10.1016/j.peptides.2011.06.005. PubMed DOI
Elbe-Bürger A. Skin architecture and function. In: Kamolz L.P., Jeschke M.G., Horch R.E., Küntscher M., Brychta P., editors. Handbook of Burns: Reconstruction and Rehabilitation Volume 2. Springer; Vienna, Austria: 2012. pp. 29–46. DOI
Biondo N.E., Argenta F.D., Rauber S.G., Caon T. How to define the experimental conditions of skin permeation assays for drugs presenting biopharmaceutical limitations? The experience with testosterone. Int. J. Pharm. 2021;607:120987. doi: 10.1016/j.ijpharm.2021.120987. PubMed DOI
Laurent A., Mistretta F., Bottigioli D., Dahel K., Goujon C., Nicolas J.F., Hennino A., Laurent P.E. Echographic measurement of skin thickness in adults by high frequency ultrasound to assess the appropriate microneedle length for intradermal delivery of vaccines. Vaccine. 2007;25:6423–6430. doi: 10.1016/j.vaccine.2007.05.046. PubMed DOI
Granieri G., Oranges T., Morganti R., Janowska A., Romanelli M., Manni E., Dini V. Ultra-high frequency ultrasound detection of the dermo-epidermal junction: Its potential role in dermatology. Exp. Dermatol. 2022;31:1863–1871. doi: 10.1111/exd.14664. PubMed DOI
Cinotti E., Bovi C., Tonini G., Labeille B., Heusèle C., Nizard C., Schnebert S., Aubailly S., Barthélémy J.C., Cambazard F., et al. Structural skin changes in elderly people investigated by reflectance confocal microscopy. J. Eur. Acad. Dermatol. Venereol. 2020;34:2652–2658. doi: 10.1111/jdv.16466. PubMed DOI
Van Mulder T.J.S., Van Nuffel D., Demolder M., De Meyer G., Moens S., Beyers K.C.L. Skin thickness measurements for optimal intradermal injections in children. Vaccine. 2020;38:763–768. doi: 10.1016/j.vaccine.2019.11.002. PubMed DOI
Firooz A., Rajabi-Estarabadi A., Zartab H., Pazhohi N., Fanian F., Janani L. The influence of gender and age on the thickness and echo-density of skin. Skin Res. Technol. 2017;23:13–20. doi: 10.1111/srt.12294. PubMed DOI
Ashcroft G.S., Mills S.J. Androgen receptor-mediated inhibition of cutaneous wound healing. J. Clin. Investig. 2002;110:615–624. doi: 10.1172/JCI0215704. PubMed DOI PMC
Jacobi U., Kaiser M., Toll R., Mangelsdorf S., Audring H., Otberg N., Sterry W., Lademann J. Porcine ear skin: An in vitro model for human skin. Skin Res. Technol. 2007;13:19–24. doi: 10.1111/j.1600-0846.2006.00179.x. PubMed DOI
Calabro K., Curtis A., Galarneau J.R., Krucker T., Bigio I.J. Gender variations in the optical properties of skin in murine animal models. J. Biomed. Opt. 2011;16:011008. doi: 10.1117/1.3525565. PubMed DOI
Otberg N., Richter H., Schaefer H., Blume-Peytavi U., Sterry W., Lademann R.J. Variations of hair follicle size and distribution in different body sites. J. Investig. Dermatol. 2004;122:14–19. doi: 10.1046/j.0022-202X.2003.22110.x. PubMed DOI
Mangelsdorf S., Vergou T., Sterry W., Lademann J., Patzelt A. Comparative study of hair follicle morphology in eight mammalian species and humans. Skin Res. Technol. 2014;20:147–154. doi: 10.1111/srt.12098. PubMed DOI
van Smeden J., Janssens M., Gooris G.S., Bouwstra J.A. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim. Biophys. Acta. 2014;1841:295–313. doi: 10.1016/j.bbalip.2013.11.006. PubMed DOI
Menon G.K., Cleary G.W., Lane M.E. The structure and function of the stratum corneum. Int. J. Pharm. 2012;435:3–9. doi: 10.1016/j.ijpharm.2012.06.005. PubMed DOI
Alexander A., Dwivedi S., Ajazuddin, Giri T.K., Saraf S., Saraf S., Tripathi D.K. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J. Control. Release. 2012;164:26–40. doi: 10.1016/j.jconrel.2012.09.017. PubMed DOI
Caselli L., Malmsten M. Skin and wound delivery systems for antimicrobial peptides. Curr. Opin. Colloid Interface Sci. 2023;65:101701. doi: 10.1016/j.cocis.2023.101701. DOI
Zhang L., Dong Z., Liu W., Wu X., He H., Lu Y., Wu W., Qi J. Novel pharmaceutical strategies for enhancing skin penetration of biomacromolecules. Pharmaceuticals. 2022;15:877. doi: 10.3390/ph15070877. PubMed DOI PMC
Kanaujia K.A., Mishra N., Rajinikanth P.S., Saraf S.A. Antimicrobial peptides as antimicrobials for wound care management: A comprehensive review. J. Drug Deliv. Sci. Technol. 2024;95:105570. doi: 10.1016/j.jddst.2024.105570. DOI
Nauroy P., Nyström A. Kallikreins: Essential epidermal messengers for regulation of the skin microenvironment during homeostasis, repair and disease. Matrix Biol. Plus. 2020;6–7:100019. doi: 10.1016/j.mbplus.2019.100019. PubMed DOI PMC
Eissa A., Diamandis E.P. Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions. Biol. Chem. 2008;389:669–680. doi: 10.1515/BC.2008.079. PubMed DOI
Ji S., Zhu Z., Sun X., Fu X. Functional hair follicle regeneration: An updated review. Signal Transduct. Target. Ther. 2021;6:66. doi: 10.1038/s41392-020-00441-y. PubMed DOI PMC
WHO The Clinical Trials Search Portal. [(accessed on 16 December 2024)]. Available online: https://trialsearch.who.int/Default.aspx.
Miranda E., Bramono K., Yunir E., Reksodiputro M.H., Suwarsa O., Rengganis I., Harahap A.R., Subekti D., Suwarto S., Hayun H., et al. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: A randomized double-blind controlled trial. Arch. Dermatol. Res. 2023;315:2623–2633. doi: 10.1007/s00403-023-02657-8. PubMed DOI PMC
Peek N.F.A.W., Nell M.J., Brand R., Jansen-Werkhoven T., van Hoogdalem E.J., Verrijk R., Vonk M.J., Wafelman A.R., Valentijn A.R.P.M., Frijns J.H.M., et al. Ototopical drops containing a novel antibacterial synthetic peptide: Safety and efficacy in adults with chronic suppurative otitis media. PLoS ONE. 2020;15:e0231573. doi: 10.1371/journal.pone.0231573. PubMed DOI PMC
Zhao Y., Zhang H., Zhao Z., Liu F., Dong M., Chen L., Shen M., Luan Z., Zhang H., Wu J., et al. Efficacy and safety of oral LL-37 against the omicron BA.5.1.3 variant of SARS-CoV-2: A randomized trial. J. Med. Virol. 2023;95:e29035. doi: 10.1002/jmv.29035. PubMed DOI
Grönberg A., Mahlapuu M., Ståhle M., Whately-Smith C., Rollman O. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: A randomized, placebo-controlled clinical trial. Wound Rep. Reg. 2014;22:613–621. doi: 10.1111/wrr.12211. PubMed DOI
Mahlapuu M., Sidorowicz A., Mikosinski J., Krzyżanowski M., Orleanski J., Twardowska-Saucha K., Nykaza M.D.A., Dyaczynski M.D.M., Belz-Lagoda M.D.B., Dziwiszek M.D.G., et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound Rep. Reg. 2021;29:938–950. doi: 10.1111/wrr.12977. PubMed DOI PMC
Rousel J., Saghari M., Pagan L., Nădăban A., Gambrah T., Theelen B., de Kam M.D., Haakman J., van der Wall H.V.D., Feiss G., et al. Treatment with the topical antimicrobial peptide omiganan in mild-to-moderate facial seborrheic dermatitis versus ketoconazole and placebo: Results of a randomized controlled proof-of-concept trial. Int. J. Mol. Sci. 2023;24:14315. doi: 10.3390/ijms241814315. PubMed DOI PMC
Niemeyer-van der Kolk T., Buters T.P., Krouwels L., Boltjes J., de Kam M.L., van der Wall H., van Alewijk D.C.J.G., van den Munckhof E.H.A., Becker M.J., Feiss G., et al. Topical antimicrobial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild to moderate atopic dermatitis in a phase 2 randomized controlled trial. J. Am. Acad. Dermatol. 2022;86:854–862. doi: 10.1016/j.jaad.2020.08.132. PubMed DOI
Niemeyer-van der Kolk T., van der Wall H., Hogendoorn G.K., Rijneveld R., Luijten S., van Alewijk D.C.J.G., van den Munckhof E.H.A., de Kam M.L., Feiss G.L., Prens E.P., et al. Pharmacodynamic effects of topical omiganan in patients with mild to moderate atopic dermatitis in a randomized, placebo-controlled, Phase II trial. Clin. Transl. Sci. 2020;13:994–1003. doi: 10.1111/cts.12792. PubMed DOI PMC
Isaacson R.E. MBI-226. Micrologix/Fujisawa. Curr. Opin. Investig. Drugs. 2003;4:999–1003. PubMed
Niemeyer-van der Kolk T., Assil S., Buters T.P., Rijsbergen M., Klaassen E.S., Feiss G., Florencia E., Prens E.P., Burggraaf J., van Doorn M.B.A., et al. Omiganan enhances imiquimod-induced inflammatory responses in skin of healthy volunteers. Clin. Transl. Sci. 2020;13:573–579. doi: 10.1111/cts.12741. PubMed DOI PMC
Rijsbergen M., Rijneveld R., Todd M., Feiss G.L., Kouwenhoven S.T.P., Quint K.D., van Alewijk D.C.J.G., de Koning M.N.C., Klaassen E.S., Burggraaf J., et al. Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions. Br. J. Clin. Pharmacol. 2020;86:2133–2143. doi: 10.1111/bcp.14181. PubMed DOI PMC
Liang L., Sonis S.T. Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck. Drug Dev. Res. 2024;85:e22188. doi: 10.1002/ddr.22188. PubMed DOI
Soligenix, Inc. [(accessed on 20 August 2024)]. Available online: https://www.soligenix.com/clinical-trials/
Dale G.E., Halabi A., Petersen-Sylla M., Wach A., Zwingelstein C. Pharmacokinetics, tolerability, and safety of murepavadin, a novel antipseudomonal antibiotic, in subjects with mild, moderate, or severe renal function impairment. Antimicrob. Agents Chemother. 2018;62:e00490-18. doi: 10.1128/AAC.00490-18. PubMed DOI PMC
Wach A., Dembowsky K., Dale G.E. Pharmacokinetics and safety of intravenous murepavadin infusion in healthy adult subjects administered single and multiple ascending doses. Antimicrob. Agents Chemother. 2018;62:e02355-17. doi: 10.1128/AAC.02355-17. PubMed DOI PMC
Kollef M., Pittet D., Sánchez García M., Chastre J., Fagon J.Y., Bonten M., Hyzy R., Fleming T.R., Fuchs H., Bellm L., et al. A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia. Am. J. Respir. Crit. Care Med. 2006;173:91–97. doi: 10.1164/rccm.200504-656OC. PubMed DOI
Giles F.J., Rodriguez R., Weisdorf D., Wingard J.R., Martin P.J., Fleming T.R., Goldberg S.L., Anaissie E.J., Bolwell B.J., Chao N.J., et al. A phase III, randomized, double-blind, placebo-controlled, study of iseganan for the reduction of stomatitis in patients receiving stomatotoxic chemotherapy. Leuk. Res. 2004;28:559–565. doi: 10.1016/j.leukres.2003.10.021. PubMed DOI
Haisma E.M., Göblyös A., Ravensbergen B., Adriaans A.E., Cordfunke R.A., Schrumpf J., Limpens R.W.A.L., Schimmel K.J.M., den Hartigh J., Hiemstra P.S., et al. Antimicrobial peptide P60.4Ac-containing creams and gel for eradication of methicillin-resistant Staphylococcus aureus from cultured skin and airway epithelial surfaces. Antimicrob. Agents Chemother. 2016;60:4063–4072. doi: 10.1128/AAC.03001-15. PubMed DOI PMC
de Breij A., Riool M., Cordfunke R.A., Malanovic N., de Boer L., Koning R.I., Ravensbergen E., Franken M., van der Heijde T., Boekema B.K., et al. The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms. Sci. Transl. Med. 2018;10:eaan4044. doi: 10.1126/scitranslmed.aan4044. Erratum in Sci. Transl. Med. 2018, 10, eaat5731. PubMed DOI
Woodburn K.W., Jaynes J.M., Clemens L.E. Evaluation of the antimicrobial peptide, RP557, for the broad-spectrum treatment of wound pathogens and biofilm. Front. Microbiol. 2019;10:1688. doi: 10.3389/fmicb.2019.01688. PubMed DOI PMC
Li B., Zhang Y., Guo Q., He S., Fan J., Xu L., Zhang Z., Wu W., Chu H. Antibacterial peptide RP557 increases the antibiotic sensitivity of Mycobacterium abscessus by inhibiting biofilm formation. Sci. Total Environ. 2022;807:151855. doi: 10.1016/j.scitotenv.2021.151855. PubMed DOI
Soligenix. [(accessed on 21 May 2024)]. Available online: https://www.soligenix.com/pipeline-programs/
North J.R., Takenaka S., Rozek A., Kielczewska A., Opal S., Morici L.A., Finlay B.B., Schaber C.J., Straube R., Donini O. A novel approach for emerging and antibiotic-resistant infections: Innate defense regulators as an agnostic therapy. J. Biotechnol. 2016;226:24–34. doi: 10.1016/j.jbiotec.2016.03.032. PubMed DOI PMC
Fritsche T.R., Rhomberg P.R., Sader H.S., Jones R.N. Antimicrobial activity of omiganan pentahydrochloride tested against contemporary bacterial pathogens commonly responsible for catheter-associated infections. J. Antimicrob. Chemother. 2008;61:1092–1098. doi: 10.1093/jac/dkn074. PubMed DOI
Toney J.H. Iseganan (IntraBiotics pharmaceuticals) Curr. Opin. Investig. Drugs. 2002;3:225–228. PubMed
Trotti A., Garden A., Warde P., Symonds P., Langer C., Redman R., Pajak T.F., Fleming T.R., Henke M., Bourhis J., et al. A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy. Int. J. Radiat. Oncol. Biol. Phys. 2004;58:674–681. doi: 10.1016/S0360-3016(03)01627-4. PubMed DOI
Donnelly J.P., Bellm L.A., Epstein J.B., Sonis S.T., Symonds R.P. Antimicrobial therapy to prevent or treat oral mucositis. Lancet Infect. Dis. 2003;3:405–412. doi: 10.1016/S1473-3099(03)00668-6. Erratum in Lancet Infect. Dis. 2003, 3, 598. PubMed DOI
BioSpace Polyphor Temporarily Halts Enrollment in the Phase III Studies of Murepavadin for the Treatment of Patients with Nosocomial Pneumonia. [(accessed on 10 June 2024)]. Available online: https://www.biospace.com/article/polyphor-temporarily-halts-enrollment-in-the-phase-iii-studies-of-murepavadin-for-the-treatment-of-patients-with-nosocomial-pneumonia/
Wang T.T., Nestel F.P., Bourdeau V., Nagai Y., Wang Q., Liao J., Tavera-Mendoza L., Lin R., Hanrahan J.W., Mader S., et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 2004;173:2909–2912. doi: 10.4049/jimmunol.173.5.2909. Erratum in J. Immunol. 2004, 173, 6490. PubMed DOI
Weber G., Heilborn J.D., Chamorro Jimenez C.I., Hammarsjo A., Törmä H., Stahle M. Vitamin D induces the antimicrobial protein hCAP18 in human skin. J. Investig. Dermatol. 2005;124:1080–1082. doi: 10.1111/j.0022-202X.2005.23687.x. PubMed DOI
Albenali L.H., Danby S., Moustafa M., Brown K., Chittock J., Shackley F., Cork M.J. Vitamin D and antimicrobial peptide levels in patients with atopic dermatitis and atopic dermatitis complicated by eczema herpeticum: A pilot study. J. Allergy Clin. Immunol. 2016;138:1715–1719.e4. doi: 10.1016/j.jaci.2016.05.039. PubMed DOI
Hata T.R., Kotol P., Jackson M., Nguyen M., Paik A., Udall D., Kanada K., Yamasaki K., Alexandrescu D., Gallo R.L. Administration of oral vitamin D induces cathelicidin production in atopic individuals. J. Allergy Clin. Immunol. 2008;122:829–831. doi: 10.1016/j.jaci.2008.08.020. PubMed DOI PMC
Chen X., Zou X., Qi G., Tang Y., Guo Y., Si J., Liang L. Roles and mechanisms of human cathelicidin LL-37 in cancer. Cell. Physiol. Biochem. 2018;47:1060–1073. doi: 10.1159/000490183. PubMed DOI
Liu P.T., Stenger S., Li H., Wenzel L., Tan B.H., Krutzik S.R., Ochoa M.T., Schauber J., Wu K., Meinken C., et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–1773. doi: 10.1126/science.1123933. PubMed DOI
Amrein K., Scherkl M., Hoffmann M., Neuwersch-Sommeregger S., Köstenberger M., Tmava Berisha A., Martucci G., Pilz S., Malle O. Vitamin D deficiency 2.0: An update on the current status worldwide. Eur. J. Clin. Nutr. 2020;74:1498–1513. doi: 10.1038/s41430-020-0558-y. PubMed DOI PMC
Yamshchikov A.V., Kurbatova E.V., Kumari M., Blumberg H.M., Ziegler T.R., Ray S.M., Tangpricha V. Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am. J. Clin. Nutr. 2010;92:603–611. doi: 10.3945/ajcn.2010.29411. PubMed DOI PMC
Kordi M., Talkhounche P.G., Vahedi H., Farrokhi N., Tabarzad M. Heterologous production of antimicrobial peptides: Notes to consider. Protein J. 2024;43:129–158. doi: 10.1007/s10930-023-10174-w. PubMed DOI
Chen N., Jiang C. Antimicrobial peptides: Structure, mechanism, and modification. Eur. J. Med. Chem. 2023;255:115377. doi: 10.1016/j.ejmech.2023.115377. PubMed DOI
Roca-Pinilla R., Lisowski L., Arís A., Garcia-Fruitós E. The future of recombinant host defense peptides. Microb. Cell Factories. 2022;21:267. doi: 10.1186/s12934-022-01991-2. PubMed DOI PMC
Wibowo D., Zhao C.X. Recent achievements and perspectives for large-scale recombinant production of antimicrobial peptides. Appl. Microbiol. Biotechnol. 2019;103:659–671. doi: 10.1007/s00253-018-9524-1. PubMed DOI
Chaudhary S., Ali Z., Mahfouz M. Molecular farming for sustainable production of clinical-grade antimicrobial peptides. Plant Biotechnol. J. 2024;22:2282–2300. doi: 10.1111/pbi.14344. PubMed DOI PMC
Deo S., Turton K.L., Kainth T., Kumar A., Wieden H.J. Strategies for improving antimicrobial peptide production. Biotechnol. Adv. 2022;59:107968. doi: 10.1016/j.biotechadv.2022.107968. PubMed DOI
Vieira Gomes A.M., Souza Carmo T., Silva Carvalho L., Mendonça Bahia F., Parachin N.S. Comparison of yeasts as hosts for recombinant protein production. Microorganisms. 2018;6:38. doi: 10.3390/microorganisms6020038. PubMed DOI PMC
Li Y. A novel protocol for the production of recombinant LL-37 expressed as a thioredoxin fusion protein. Protein Expr. Purif. 2012;81:201–210. doi: 10.1016/j.pep.2011.10.011. PubMed DOI
Li Y. Production of human antimicrobial peptide LL-37 in Escherichia coli using a thioredoxin-SUMO dual fusion system. Protein Expr. Purif. 2013;87:72–78. doi: 10.1016/j.pep.2012.10.008. PubMed DOI
Colomina-Alfaro L., Marchesan S., Stamboulis A., Bandiera A. Smart tools for antimicrobial peptides expression and application: The elastic perspective. Biotechnol. Bioeng. 2023;120:323–332. doi: 10.1002/bit.28283. PubMed DOI
Zhao C.X., Dwyer M.D., Yu A.L., Wu Y., Fang S., Middelberg A.P. A simple and low-cost platform technology for producing pexiganan antimicrobial peptide in E. coli. Biotechnol. Bioeng. 2015;112:957–964. doi: 10.1002/bit.25505. PubMed DOI
Dwyer M.D., Brech M., Yu L., Middelberg A.P.J. Intensified expression and purification of a recombinant biosurfactant protein. Chem. Eng. Sci. 2014;105:12–21. doi: 10.1016/j.ces.2013.10.024. DOI
Sun B., Wibowo D., Middelberg A.P.J., Zhao C.X. Cost-effective downstream processing of recombinantly produced pexiganan peptide and its antimicrobial activity. AMB Express. 2018;8:6. doi: 10.1186/s13568-018-0541-3. PubMed DOI PMC
Sousa D.A., Mulder K.C.L., Nobre K.S., Parachin N.S., Franco O.L. Production of a polar fish antimicrobial peptide in Escherichia coli using an ELP-intein tag. J. Biotechnol. 2016;234:83–89. doi: 10.1016/j.jbiotec.2016.07.021. PubMed DOI
Colomina-Alfaro L., Sist P., Marchesan S., Urbani R., Stamboulis A., Bandiera A. A versatile elastin-like carrier for bioactive antimicrobial peptide production and delivery. Macromol. Biosci. 2024;24:e2300236. doi: 10.1002/mabi.202470007. PubMed DOI
Holásková E., Galuszka P., Mičúchová A., Šebela M., Öz M.T., Frébort I. Molecular farming in barley: Development of a novel production platform to produce human antimicrobial peptide LL-37. Biotechnol. J. 2018;13:1700628. doi: 10.1002/biot.201700628. PubMed DOI
Pane K., Durante L., Pizzo E., Varcamonti M., Zanfardino A., Sgambati V., Di Maro A., Carpentieri A., Izzo V., Di Donato A., et al. Rational design of a carrier protein for the production of recombinant toxic peptides in Escherichia coli. PLoS ONE. 2016;11:e0146552. doi: 10.1371/journal.pone.0146552. PubMed DOI PMC
He Q., Fu A., Li T. Expression and one-step purification of the antimicrobial peptide cathelicidin-BF using the intein system in Bacillus subtilis. J. Ind. Microbiol. Biotechnol. 2015;42:647–653. doi: 10.1007/s10295-014-1582-5. PubMed DOI
Zhou N., An T., Zhang Y., Zhao G., Wei C., Shen X., Li F., Wang X. Improving photocleavage efficiency of photocleavable protein for antimicrobial peptide histatin 1 expression. Protein Pept. Lett. 2024;31:141–152. doi: 10.2174/0109298665276722231212053009. PubMed DOI
Li Y., Li X., Wang G. Cloning, expression, isotope labeling, and purification of human antimicrobial peptide LL-37 in Escherichia coli for NMR studies. Protein Expr. Purif. 2006;47:498–505. doi: 10.1016/j.pep.2005.10.022. PubMed DOI
Wei X., Wu R., Zhang L., Ahmad B., Si D., Zhang R. Expression, purification, and characterization of a novel hybrid peptide with potent antibacterial activity. Molecules. 2018;23:1491. doi: 10.3390/molecules23061491. PubMed DOI PMC
Deng T., Ge H., He H., Liu Y., Zhai C., Feng L., Yi L. The heterologous expression strategies of antimicrobial peptides in microbial systems. Protein Expr. Purif. 2017;140:52–59. doi: 10.1016/j.pep.2017.08.003. PubMed DOI
Morin K.M., Arcidiacono S., Beckwitt R., Mello C.M. Recombinant expression of indolicidin concatamers in Escherichia coli. Appl. Microbiol. Biotechnol. 2006;70:698–704. doi: 10.1007/s00253-005-0132-5. PubMed DOI
Xiao S., Gao Y., Wang X., Shen W., Wang J., Zhou X., Cai M., Zhang Y. Peroxisome-targeted and tandem repeat multimer expressions of human antimicrobial peptide LL37 in Pichia pastoris. Prep. Biochem. Biotechnol. 2017;47:229–235. doi: 10.1080/10826068.2016.1201684. PubMed DOI
Dong X., Shan H., Wang S., Jiang Z., Wang S., Qin Z. High expression of antimicrobial peptides cathelicidin-BF in Pichia pastoris and verification of its activity. Front. Microbiol. 2023;14:1153365. doi: 10.3389/fmicb.2023.1153365. PubMed DOI PMC
Wei X.B., Wu R.J., Si D.Y., Liao X.D., Zhang L.L., Zhang R.J. Novel hybrid peptide cecropin A (1-8)-LL37 (17-30) with potential antibacterial activity. Int. J. Mol. Sci. 2016;17:983. doi: 10.3390/ijms17070983. PubMed DOI PMC
Abbasi M., Behmard E., Yousefi M.H., Shekarforoush S.S., Mahmoodi S. Expression, purification and investigation of antibacterial activity of a novel hybrid peptide LL37/hBD-129 by applied comprehensive computational and experimental approaches. Arch. Microbiol. 2023;205:199. doi: 10.1007/s00203-023-03529-5. PubMed DOI
Zhao L., Li L., Hu M., Fang Y., Dong N., Shan A. Heterologous expression of the novel dimeric antimicrobial peptide LIG in Pichia pastoris. J. Biotechnol. 2024;381:19–26. doi: 10.1016/j.jbiotec.2023.12.015. PubMed DOI
Roca-Pinilla R., López-Cano A., Saubi C., Garcia-Fruitós E., Arís A. A new generation of recombinant polypeptides combines multiple protein domains for effective antimicrobial activity. Microb. Cell Factories. 2020;19:122. doi: 10.1186/s12934-020-01380-7. PubMed DOI PMC
Holásková E., Galuszka P., Frébort I., Oz M.T. Antimicrobial peptide production and plant-based expression systems for medical and agricultural biotechnology. Biotechnol. Adv. 2015;33:1005–1023. doi: 10.1016/j.biotechadv.2015.03.007. PubMed DOI
Shanmugaraj B., Bulaon C.J.I., Malla A., Phoolcharoen W. Biotechnological insights on the expression and production of antimicrobial peptides in plants. Molecules. 2021;26:4032. doi: 10.3390/molecules26134032. PubMed DOI PMC
Gerszberg A., Hnatuszko-Konka K. Compendium on food crop plants as a platform for pharmaceutical protein production. Int. J. Mol. Sci. 2022;23:3236. doi: 10.3390/ijms23063236. PubMed DOI PMC
Morassutti C., De Amicis F., Skerlavaj B., Zanetti M., Marchetti S. Production of a recombinant antimicrobial peptide in transgenic plants using a modified VMA intein expression system. FEBS Lett. 2002;519:141–146. doi: 10.1016/S0014-5793(02)02741-2. PubMed DOI
Jung Y.J., Lee S.Y., Moon Y.S., Kang K.K. Enhanced resistance to bacterial and fungal pathogens by overexpression of a human cathelicidin antimicrobial peptide (hCAP18/LL-37) in Chinese cabbage. Plant Biotechnol. Rep. 2012;6:39–46. doi: 10.1007/s11816-011-0193-0. PubMed DOI PMC
Jung Y.J. Enhanced resistance to bacterial pathogen in transgenic tomato plants expressing cathelicidin antimicrobial peptide. Biotechnol. Bioprocess Eng. 2013;18:615–624. doi: 10.1007/s12257-013-0392-3. DOI
Lee I.H., Jung Y.J., Cho Y.G., Nou I.S., Huq M.A., Nogoy F.M., Kang K.K. SP-LL-37, human antimicrobial peptide, enhances disease resistance in transgenic rice. PLoS ONE. 2017;12:e0172936. doi: 10.1371/journal.pone.0172936. PubMed DOI PMC
Lee S.B., Li B., Jin S., Daniell H. Expression and characterization of antimicrobial peptides Retrocyclin-101 and Protegrin-1 in chloroplasts to control viral and bacterial infections. Plant Biotechnol. J. 2011;9:100–115. doi: 10.1111/j.1467-7652.2010.00538.x. PubMed DOI PMC
Patiño-Rodríguez O., Ortega-Berlanga B., Llamas-González Y.Y., Mario A., Flores-Valdez M.A., Herrera-Díaz A., Montes-de-Octa-Luna R., Korban S., Alpuche-Solís A. Transient expression and characterization of the antimicrobial peptide protegrin-1 in Nicotiana tabacum for control of bacterial and fungal mammalian pathogens. Plant Cell Tissue Organ Cult. 2013;115:99–106. doi: 10.1007/s11240-013-0344-9. DOI
Lau O.S., Sun S.S. Plant seeds as bioreactors for recombinant protein production. Biotechnol. Adv. 2009;27:1015–1022. doi: 10.1016/j.biotechadv.2009.05.005. PubMed DOI
Mirzaee M., Holásková E., Mičúchová A., Kopečný D.J., Osmani Z., Frébort I. Long-lasting stable expression of human LL-37 antimicrobial peptide in transgenic barley plants. Antibiotics. 2021;10:898. doi: 10.3390/antibiotics10080898. PubMed DOI PMC
Bundó M., Shi X., Vernet M., Marcos J.F., López-García B., Coca M. Rice seeds as biofactories of rationally designed and cell-penetrating antifungal PAF peptides. Front. Plant Sci. 2019;10:731. doi: 10.3389/fpls.2019.00731. PubMed DOI PMC
Peng C.A., Kozubowski L., Marcotte W.R., Jr. Advances in plant-derived scaffold proteins. Front. Plant Sci. 2020;11:122. doi: 10.3389/fpls.2020.00122. PubMed DOI PMC
Elmowafy M. Skin penetration/permeation success determinants of nanocarriers: Pursuit of a perfect formulation. Colloids Surf. B: Biointerfaces. 2021;203:111748. doi: 10.1016/j.colsurfb.2021.111748. PubMed DOI
Lane M.E. Skin penetration enhancers. Int. J. Pharm. 2013;447:12–21. doi: 10.1016/j.ijpharm.2013.02.040. PubMed DOI
Gera S., Kankuri E., Kogermann K. Antimicrobial peptides—Unleashing their therapeutic potential using nanotechnology. Pharmacol. Ther. 2022;232:107990. doi: 10.1016/j.pharmthera.2021.107990. PubMed DOI
Liu T., Chen M., Fu J., Sun Y., Lu C., Quan G., Pan X., Wu C. Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs. Acta Pharm. Sin. B. 2021;11:2326–2343. doi: 10.1016/j.apsb.2021.03.003. PubMed DOI PMC
Wong T.W. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery. J. Control. Release. 2014;193:257–269. doi: 10.1016/j.jconrel.2014.04.045. PubMed DOI
Fumakia M., Ho E.A. Nanoparticles encapsulated with LL37 and serpin A1 promotes wound healing and synergistically enhances antibacterial activity. Mol. Pharm. 2016;13:2318–2331. doi: 10.1021/acs.molpharmaceut.6b00099. PubMed DOI
Gatti J.W., Smithgall M.C., Paranjape S.M., Rolfes R.J., Paranjape M. Using electrospun poly(ethylene-oxide) nanofibers for improved retention and efficacy of bacteriolytic antibiotics. Biomed. Microdevices. 2013;15:887–893. doi: 10.1007/s10544-013-9777-5. PubMed DOI
Patzelt A., Lademann J. The increasing importance of the hair follicle route in dermal and transdermal drug delivery. In: Dragicevic N., Maibach H.I., editors. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Drug Manipulation Strategies and Vehicle Effects. Springer; Berlin/Heidelberg, Germany: 2015. pp. 43–53. DOI
Schneider-Rauber G., Argenta D.F., Caon T. Emerging technologies to target drug delivery to the skin—The role of crystals and carrier-based systems in the case study of dapsone. Pharm. Res. 2020;37:240. doi: 10.1007/s11095-020-02951-4. PubMed DOI
Fang C.L., Aljuffali I.A., Li Y.C., Fang J.Y. Delivery and targeting of nanoparticles into hair follicles. Ther. Deliv. 2014;5:991–1006. doi: 10.4155/tde.14.61. PubMed DOI
Lademann J., Richter H., Schanzer S., Knorr F., Meinke M., Sterry W., Patzelt A. Penetration and storage of particles in human skin: Perspectives and safety aspects. Eur. J. Pharm. Biopharm. 2011;77:465–468. doi: 10.1016/j.ejpb.2010.10.015. PubMed DOI
Pelikh O., Eckert R.W., Pinnapireddy S.R., Keck C.M. Hair follicle targeting with curcumin nanocrystals: Influence of the formulation properties on the penetration efficacy. J. Control. Release. 2021;329:598–613. doi: 10.1016/j.jconrel.2020.09.053. PubMed DOI
Chin J.S., Madden L., Chew S.Y., Becker D.L. Drug therapies and delivery mechanisms to treat perturbed skin wound healing. Adv. Drug Deliv. Rev. 2019;149–150:2–18. doi: 10.1016/j.addr.2019.03.006. PubMed DOI
Kopecki Z. Development of next-generation antimicrobial hydrogel dressing to combat burn wound infection. Biosci. Rep. 2021;41:BSR20203404. doi: 10.1042/BSR20203404. PubMed DOI PMC
Peppas N.A., Bures P., Leobandung W., Ichikawa H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 2000;50:27–46. doi: 10.1016/S0939-6411(00)00090-4. PubMed DOI
Al Musaimi O., Lombardi L., Williams D.R., Albericio F. Strategies for improving peptide stability and delivery. Pharmaceuticals. 2022;15:1283. doi: 10.3390/ph15101283. PubMed DOI PMC
Răileanu M., Borlan R., Campu A., Janosi L., Turcu I., Focsan M., Bacalum M. No country for old antibiotics! Antimicrobial peptides (AMPs) as next-generation treatment for skin and soft tissue infection. Int. J. Pharm. 2023;642:123169. doi: 10.1016/j.ijpharm.2023.123169. PubMed DOI
Rezaei N., Hamidabadi H.G., Khosravimelal S., Zahiri M., Ahovan Z.A., Bojnordi M.N., Eftekhari B.S., Hashemi A., Ganji F., Darabi S., et al. Antimicrobial peptides-loaded smart chitosan hydrogel: Release behavior and antibacterial potential against antibiotic resistant clinical isolates. Int. J. Biol. Macromol. 2020;164:855–862. doi: 10.1016/j.ijbiomac.2020.07.011. PubMed DOI
Silva J.P., Dhall S., Garcia M., Chan A., Costa C., Gama M., Martins-Green M. Improved burn wound healing by the antimicrobial peptide LLKKK18 released from conjugates with dextrin embedded in a carbopol gel. Acta Biomater. 2015;26:249–262. doi: 10.1016/j.actbio.2015.07.043. PubMed DOI
Grek C.L., Prasad G.M., Viswanathan V., Armstrong D.G., Gourdie R.G., Ghatnekar G.S. Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers: A multicenter, randomized trial. Wound Repair Regen. 2015;23:203–212. doi: 10.1111/wrr.12275. PubMed DOI PMC
Laverty G., Gorman S.P., Gilmore B.F. Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections. J. Biomed. Mater. Res. A. 2012;100A:1803–1814. doi: 10.1002/jbm.a.34132. PubMed DOI
Zhou C., Li P., Qi X., Sharif A.R., Poon Y.F., Cao Y., Chang M.W., Leong S.S., Chan-Park M.B. A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-l-lysine. Biomaterials. 2011;32:2704–2712. doi: 10.1016/j.biomaterials.2010.12.040. PubMed DOI
Li X., Fan R., Tong A., Yang M., Deng J., Zhou L., Zhang X., Guo G. In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing. Int. J. Pharm. 2015;495:560–571. doi: 10.1016/j.ijpharm.2015.09.005. PubMed DOI
Su Y., Wang H., Mishra B., Lakshmaiah Narayana J., Jiang J., Reilly D.A., Hollins R.R., Carlson M.A., Wang G., Xie J. Nanofiber dressings topically delivering molecularly engineered human cathelicidin peptides for the treatment of biofilms in chronic wounds. Mol. Pharm. 2019;16:2011–2020. doi: 10.1021/acs.molpharmaceut.8b01345. PubMed DOI
Yan X., Fang W.W., Xue J., Sun T.C., Dong L., Zha Z., Qian H., Song Y.H., Zhang M., Gong X., et al. Thermoresponsive in situ forming hydrogel with sol-gel irreversibility for effective methicillin-resistant Staphylococcus aureus infected wound healing. ACS Nano. 2019;13:10074–10084. doi: 10.1021/acsnano.9b02845. PubMed DOI
Sabzevari R., Roushandeh A.M., Mehdipour A., Alini M., Roudkenar M.H. SA/G hydrogel containing hCAP-18/LL-37-engineered WJ-MSCs-derived conditioned medium promoted wound healing in rat model of excision injury. Life Sci. 2020;261:118381. doi: 10.1016/j.lfs.2020.118381. PubMed DOI
Patrulea V., Borchard G., Jordan O. An update on antimicrobial peptides (AMPs) and their delivery strategies for wound infections. Pharmaceutics. 2020;12:840. doi: 10.3390/pharmaceutics12090840. PubMed DOI PMC
Xia X., Song S., Zhang S., Wang W., Zhou J., Fan B., Li L., Dong H., Luo C., Li B., et al. The synergy of thanatin and cathelicidin-BF-15a3 combats Escherichia coli O157:H7. Int. J. Food Microbiol. 2023;386:110018. doi: 10.1016/j.ijfoodmicro.2022.110018. PubMed DOI
Farzi N., Oloomi M., Bahramali G., Siadat S.D., Bouzari S. Antibacterial properties and efficacy of LL-37 fragment GF-17D3 and scolopendin A2 peptides against resistant clinical strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii in vitro and in vivo model studies. Probiotics Antimicrob. Proteins. 2024;16:796–814. doi: 10.1007/s12602-023-10070-w. PubMed DOI
Jiang W., Sunkara L.T., Zeng X., Deng Z., Myers S.M., Zhang G. Differential regulation of human cathelicidin LL-37 by free fatty acids and their analogs. Peptides. 2013;50:129–138. doi: 10.1016/j.peptides.2013.10.008. PubMed DOI
Steinstraesser L., Lam M.C., Jacobsen F., Porporato P.E., Chereddy K.K., Becerikli M., Stricker I., Hancock R.E., Lehnhardt M., Sonveaux P., et al. Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing. Mol. Ther. 2014;22:734–742. doi: 10.1038/mt.2013.258. PubMed DOI PMC
Thomas-Virnig C.L., Centanni J.M., Johnston C.E., He L.K., Schlosser S.J., Van Winkle K.F., Chen R., Gibson A.L., Szilagyi A., Li L., et al. Inhibition of multidrug-resistant Acinetobacter baumannii by nonviral expression of hCAP-18 in a bioengineered human skin tissue. Mol. Ther. 2009;17:562–569. doi: 10.1038/mt.2008.289. PubMed DOI PMC
Mahlapuu M., Björn C., Ekblom J. Antimicrobial peptides as therapeutic agents: Opportunities and challenges. Crit. Rev. Biotechnol. 2020;40:978–992. doi: 10.1080/07388551.2020.1796576. PubMed DOI
Kumar P., Kizhakkedathu J.N., Straus S.K. Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules. 2018;8:4. doi: 10.3390/biom8010004. PubMed DOI PMC
Maturana P., Martinez M., Noguera M.E., Santos N.C., Disalvo E.A., Semorile L., Maffia P.C., Hollmann A. Lipid selectivity in novel antimicrobial peptides: Implication on antimicrobial and hemolytic activity. Colloids Surf. B Biointerfaces. 2017;153:152–159. doi: 10.1016/j.colsurfb.2017.02.003. PubMed DOI
Mishra B., Lakshmaiah Narayana J., Lushnikova T., Zhang Y., Golla R.M., Zarena D., Wang G. Sequence permutation generates peptides with different antimicrobial and antibiofilm activities. Pharmaceuticals. 2020;13:271. doi: 10.3390/ph13100271. PubMed DOI PMC
Wang X., Mishra B., Lushnikova T., Narayana J.L., Wang G. Amino acid composition determines peptide activity spectrum and hot-spot-based design of merecidin. Adv. Biosyst. 2018;2:1700259. doi: 10.1002/adbi.201700259. PubMed DOI PMC
Biondi B., de Pascale L., Mardirossian M., Di Stasi A., Favaro M., Scocchi M., Peggion C. Structural and biological characterization of shortened derivatives of the cathelicidin PMAP-36. Sci. Rep. 2023;13:15132. doi: 10.1038/s41598-023-41945-1. PubMed DOI PMC
Strömstedt A.A., Pasupuleti M., Schmidtchen A., Malmsten M. Evaluation of strategies for improving proteolytic resistance of antimicrobial peptides by using variants of EFK17, an internal segment of LL-37. Antimicrob. Agents Chemother. 2009;53:593–602. doi: 10.1128/AAC.00477-08. PubMed DOI PMC
Jangpromma N., Konkchaiyaphum M., Punpad A., Sosiangdi S., Daduang S., Klaynongsruang S., Tankrathok A. Rational design of RN15m4 cathelin domain-based peptides from siamese crocodile cathelicidin improves antimicrobial activity. Appl. Biochem. Biotechnol. 2023;195:1096–1108. doi: 10.1007/s12010-022-04210-1. PubMed DOI
Gunasekera S., Muhammad T., Strömstedt A.A., Rosengren K.J., Göransson U. Backbone cyclization and dimerization of LL-37-derived peptides enhance antimicrobial activity and proteolytic stability. Front. Microbiol. 2020;11:168. doi: 10.3389/fmicb.2020.00168. PubMed DOI PMC
Dean S.N., Bishop B.M., van Hoek M.L. Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus. BMC Microbiol. 2011;11:114. doi: 10.1186/1471-2180-11-114. PubMed DOI PMC
McClements D.J. Encapsulation, protection, and delivery of bioactive proteins and peptides using nanoparticle and microparticle systems: A review. Adv. Colloid Interface Sci. 2018;253:1–22. doi: 10.1016/j.cis.2018.02.002. PubMed DOI
Chereddy K.K., Her C.H., Comune M., Moia C., Lopes A., Porporato P.E., Vanacker J., Lam M.C., Steinstraesser L., Sonveaux P., et al. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing. J. Control. Release. 2014;194:138–147. doi: 10.1016/j.jconrel.2014.08.016. PubMed DOI
Sun T., Zhan B., Zhang W., Qin D., Xia G., Zhang H., Peng M., Li S.A., Zhang Y., Gao Y., et al. Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing. Int. J. Nanomed. 2018;13:5771–5786. doi: 10.2147/IJN.S156206. PubMed DOI PMC
Lozeau L.D., Grosha J., Kole D., Prifti F., Dominko T., Camesano T.A., Rolle M.W. Collagen tethering of synthetic human antimicrobial peptides cathelicidin LL37 and its effects on antimicrobial activity and cytotoxicity. Acta Biomater. 2017;52:9–20. doi: 10.1016/j.actbio.2016.12.047. PubMed DOI
Boge L., Hallstensson K., Ringstad L., Johansson J., Andersson T., Davoudi M., Larsson P.T., Mahlapuu M., Håkansson J., Andersson M. Cubosomes for topical delivery of the antimicrobial peptide LL-37. Eur. J. Pharm. Biopharm. 2019;134:60–67. doi: 10.1016/j.ejpb.2018.11.009. PubMed DOI
Gontsarik M., Buhmann M.T., Yaghmur A., Ren Q., Maniura-Weber K., Salentinig S. Antimicrobial peptide-driven colloidal transformations in liquid-crystalline nanocarriers. J. Phys. Chem. Lett. 2016;7:3482–3486. doi: 10.1021/acs.jpclett.6b01622. PubMed DOI
Ricardo F., Pradilla D., Cruz J.C., Alvarez O. Emerging emulsifiers: Conceptual basis for the identification and rational design of peptides with surface activity. Int. J. Mol. Sci. 2021;22:4615. doi: 10.3390/ijms22094615. PubMed DOI PMC
Bouwstra J.A., Honeywell-Nguyen P.L., Gooris G.S., Ponec M. Structure of the skin barrier and its modulation by vesicular formulations. Prog. Lipid Res. 2003;42:1–36. doi: 10.1016/S0163-7827(02)00028-0. PubMed DOI
Pierre M.B.R., dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch. Dermatol. Res. 2011;303:607–621. doi: 10.1007/s00403-011-1166-4. PubMed DOI
Taylor T.M., Gaysinsky S., Davidson P.M., Bruce B.D., Weiss J. Characterization of antimicrobial-bearing liposomes by ζ-potential, vesicle size, and encapsulation efficiency. Food Biophys. 2007;2:1–9. doi: 10.1007/s11483-007-9023-x. DOI
Bilati U., Allémann E., Doelker E. Strategic approaches for overcoming peptide and protein instability within biodegradable nano- and microparticles. Eur. J. Pharm. Biopharm. 2005;59:375–388. doi: 10.1016/j.ejpb.2004.10.006. PubMed DOI
Pham N.B., Meng W.S. Protein aggregation and immunogenicity of biotherapeutics. Int. J. Pharm. 2020;585:119523. doi: 10.1016/j.ijpharm.2020.119523. PubMed DOI PMC
Elsayed A., Jaber N., Al-Remawi M., Abu-Salah K. From cell factories to patients: Stability challenges in biopharmaceuticals manufacturing and administration with mitigation strategies. Int. J. Pharm. 2023;645:123360. doi: 10.1016/j.ijpharm.2023.123360. PubMed DOI
Solè I., Pey C.M., Maestro A., González C., Porras M., Solans C., Gutiérrez J.M. Nano-emulsions prepared by the phase inversion composition method: Preparation variables and scale up. J. Colloid Interface Sci. 2010;344:417–423. doi: 10.1016/j.jcis.2009.11.046. PubMed DOI
Solans C., Solé I. Nano-emulsions: Formation by low-energy methods. Curr. Opin. Colloid Interface Sci. 2012;17:246–254. doi: 10.1016/j.cocis.2012.07.003. DOI
Solans C., Morales D., Homs M. Spontaneous emulsification. Curr. Opin. Colloid Interface Sci. 2016;22:88–93. doi: 10.1016/j.cocis.2016.03.002. DOI
Cole J.N., Nizet V. Bacterial evasion of host antimicrobial peptide defenses. Microbiol. Spectr. 2016;4:10. doi: 10.1128/microbiolspec.VMBF-0006-2015. PubMed DOI PMC
LaRock C.N., Nizet V. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens. Biochim. Biophys. Acta Biomembr. 2015;1848:3047–3054. doi: 10.1016/j.bbamem.2015.02.010. PubMed DOI PMC
Moskowitz S.M., Ernst R.K., Miller S.I. PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to Lipid A. J. Bacteriol. 2004;186:575–579. doi: 10.1128/JB.186.2.575-579.2004. PubMed DOI PMC
Lysenko E.S., Gould J., Bals R., Wilson J.M., Weiser J.N. Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect. Immun. 2000;68:1664–1671. doi: 10.1128/IAI.68.3.1664-1671.2000. PubMed DOI PMC
Guina T., Yi E.C., Wang H., Hackett M., Miller S.I. A PhoP-regulated outer membrane protease of Salmonella enterica serovar Typhimurium promotes resistance to alpha-helical antimicrobial peptides. J. Bacteriol. 2000;182:4077–4086. doi: 10.1128/JB.182.14.4077-4086.2000. PubMed DOI PMC
Lewis L.A., Choudhury B., Balthazar J.T., Martin L.E., Ram S., Rice P.A., Stephens D.S., Carlson R., Shafer W.M. Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum. Infect. Immun. 2009;77:1112–1120. doi: 10.1128/IAI.01280-08. PubMed DOI PMC
Harper M., Wright A., Michael F.S., Li J., Lucas D.D., Ford M., Adler B., Cox A.D., Boyce J.D. Characterization of two novel lipopolysaccharide phosphoethanolamine transferases in Pasteurella multocida and their role in resistance to cathelicidin-2. Infect. Immun. 2017;85:e00557-17. doi: 10.1128/IAI.00557-17. PubMed DOI PMC
Falord M., Mäder U., Hiron A., Dbarbouillé M., Msadek T. Investigation of the Staphylococcus aureus GraSR regulon reveals novel links to virulence, stress response and cell wall signal transduction pathways. PLoS ONE. 2011;6:e21323. doi: 10.1371/journal.pone.0021323. PubMed DOI PMC
Falord M., Karimova G., Hiron A., Msadeka T. GraXSR proteins interact with the VraFG ABC transporter to form a five-component system required for cationic antimicrobial peptide sensing and resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 2012;56:1047–1058. doi: 10.1128/AAC.05054-11. PubMed DOI PMC
Golla R.M., Mishra B., Dang X., Lakshmaiah Narayana J., Li A., Xu L., Wang G. Resistome of Staphylococcus aureus in response to human cathelicidin LL-37 and its engineered antimicrobial peptides. ACS Infect. Dis. 2020;6:1866–1881. doi: 10.1021/acsinfecdis.0c00112. PubMed DOI PMC
Nishi H., Komatsuzawa H., Fujiwara T., McCallum N., Sugai M. Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus. Antimicrob. Agents Chemother. 2004;48:4800–4807. doi: 10.1128/AAC.48.12.4800-4807.2004. PubMed DOI PMC
Abachin E., Poyart C., Pellegrini E., Milohanic E., Fiedler F., Berche P., Trieu-Cuot P. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 2002;43:1–14. doi: 10.1046/j.1365-2958.2002.02723.x. PubMed DOI
Poyart C., Pellegrini E., Marceau M., Baptista M., Jaubert F., Lamy M.C., Trieu-Cuot P. Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol. Microbiol. 2003;49:1615–1625. doi: 10.1046/j.1365-2958.2003.03655.x. PubMed DOI
Cao M., Helmann J.D. The Bacillus subtilis extracytoplasmic-function σX factor regulates modification of the cell envelope and resistance to cationic antimicrobial peptides. J. Bacteriol. 2004;186:1136–1146. doi: 10.1128/JB.186.4.1136-1146.2004. PubMed DOI PMC
Saar-Dover R., Bitler A., Nezer R., Shmuel-Galia L., Firon A., Shimoni E., Trieu-Cuot P., Shai Y. D-alanylation of lipoteichoic acids confers resistance to cationic peptides in group B Streptococcus by increasing the cell wall density. PLoS Pathog. 2012;8:e1002891. doi: 10.1371/annotation/05894f00-6d95-4b7a-aff1-2e008d2a864f. PubMed DOI PMC
Hamilton A., Popham D.L., Carl D.J., Lauth X., Nizet V., Jones A.L. Penicillin-binding protein 1a promotes resistance of group B Streptococcus to antimicrobial peptides. Infect. Immun. 2006;74:6179–6187. doi: 10.1128/IAI.00895-06. PubMed DOI PMC
Meireles D., Pombinho R., Carvalho F., Sousa S., Cabanes D. Listeria monocytogenes wall teichoic acid glycosylation promotes surface anchoring of virulence factors, resistance to antimicrobial peptides, and decreased susceptibility to antibiotics. Pathogens. 2020;9:290. doi: 10.3390/pathogens9040290. PubMed DOI PMC
Schmidtchen A., Frick I.M., Andersson E., Tapper H., Björck L. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol. Microbiol. 2002;46:157–168. doi: 10.1046/j.1365-2958.2002.03146.x. PubMed DOI
Barańska-Rybak W., Sonesson A., Nowicki R., Schmidtchen A. Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids. J. Antimicrob. Chemother. 2006;57:260–265. doi: 10.1093/jac/dki460. PubMed DOI
Sieprawska-Lupa M., Mydel P., Krawczyk K., Wójcik K., Puklo M., Lupa B., Suder P., Silberring J., Reed M., Pohl J., et al. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob. Agents Chemother. 2004;48:4673–4679. doi: 10.1128/AAC.48.12.4673-4679.2004. PubMed DOI PMC
Shinnar A.E., Butler K.L., Park H.J. Cathelicidin family of antimicrobial peptides: Proteolytic processing and protease resistance. Bioorg. Chem. 2003;31:425–436. doi: 10.1016/S0045-2068(03)00080-4. PubMed DOI
Braff M.H., Jones A.L., Skerrett S.J., Rubens C.E. Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. J. Infect. Dis. 2007;195:1365–1372. doi: 10.1086/513277. PubMed DOI PMC
Åkessont P., Sjöholm A.G., Björck L. Protein SIC, a novel extracellular protein of Streptococcus pyogenes interfering with complement function. J. Biol. Chem. 1996;271:1081–1088. doi: 10.1074/jbc.271.2.1081. PubMed DOI
Frick I.M., Åkesson P., Rasmussen M., Schmidtchen A., Björck L. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J. Biol. Chem. 2003;278:16561–16566. doi: 10.1074/jbc.M301995200. PubMed DOI
Ghosh P. The nonideal coiled coil of M protein and its multifarious functions in pathogenesis. Adv. Exp. Med. Biol. 2011;715:197–211. doi: 10.1007/978-94-007-0940-9_12. PubMed DOI PMC
LaRock C.N., Döhrmann S., Todd J., Corriden R., Olson J., Johannssen T., Lepenies B., Gallo R.L., Ghosh P., Nizet V. Group A streptococcal M1 protein sequesters cathelicidin to evade innate immune killing. Cell Host Microbe. 2015;18:471–477. doi: 10.1016/j.chom.2015.09.004. PubMed DOI PMC
Keo T., Collins J., Kunwar P., Blaser M.J., Iovine N.M. Campylobacter capsule and lipooligosaccharide confer resistance to serum and cationic antimicrobials. Virulence. 2011;2:30–40. doi: 10.4161/viru.2.1.14752. PubMed DOI PMC
Spinosa M.R., Progida C., Talà A., Cogli L., Alifano P., Bucci C. The Neisseria meningitidis capsule is important for intracellular survival in human cells. Infect. Immun. 2007;75:3594–3603. doi: 10.1128/IAI.01945-06. PubMed DOI PMC
Cole J.N., Pence M.A., von Köckritz-Blickwede M., Hollands A., Gallo R.L., Walker M.J., Nizet V. M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 Group A Streptococcus. mBio. 2010;1:e00191-10. doi: 10.1128/mBio.00191-10. PubMed DOI PMC
Von Köckritz-Blickwede M., Nizet V. Innate immunity turned inside-out: Antimicrobial defense by phagocyte extracellular traps. J. Mol. Med. 2009;87:775–783. doi: 10.1007/s00109-009-0481-0. PubMed DOI PMC
Walker M.J., Hollands A., Sanderson-Smith M.L., Cole J.N., Kirk J.K., Henningham A., McArthur J.D., Dinkla K., Aziz R.K., Kansal R.G., et al. DNase Sda1 provides selection pressure for a switch to invasive Group A streptococcal infection. Nat. Med. 2007;13:981–985. doi: 10.1038/nm1612. PubMed DOI
Derré-Bobillot A., Cortes-Perez N.G., Yamamoto Y., Kharrat P., Couvé E., Da Cunha V., Decker P., Boissier M.C., Escartin F., Cesselin B., et al. Nuclease A (Gbs0661), an extracellular nuclease of Streptococcus agalactiae, attacks the neutrophil extracellular traps and is needed for full virulence. Mol. Microbiol. 2013;89:518–531. doi: 10.1111/mmi.12295. PubMed DOI
Beiter K., Wartha F., Albiger B., Normark S., Zychlinsky A., Henriques-Normark B. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr. Biol. 2006;16:401–407. doi: 10.1016/j.cub.2006.01.056. PubMed DOI
Berends E.T.M., Horswill A.R., Haste N.M., Monestier M., Nizet V., Von Köckritz-Blickwede M. Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps. J. Innate Immun. 2010;2:576–586. doi: 10.1159/000319909. PubMed DOI PMC
Guilhelmelli F., Vilela N., Albuquerque P., Derengowski L.S., Silva-Pereira I., Kyaw C.M. Antibiotic development challenges: The various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front. Microbiol. 2013;4:353. doi: 10.3389/fmicb.2013.00353. PubMed DOI PMC
Handing J.W., Ragland S.A., Bharathan U.V., Criss A.K. The MtrCDE efflux pump contributes to survival of Neisseria gonorrhoeae from human neutrophils and their antimicrobial components. Front. Microbiol. 2018;9:2688. doi: 10.3389/fmicb.2018.02688. PubMed DOI PMC
Tzeng Y.L., Ambrose K.D., Zughaier S., Zhou X., Miller Y.K., Shafer W.M., Stephens D.S. Cationic antimicrobial peptide resistance in Neisseria meningitidis. J. Bacteriol. 2005;187:5387–5396. doi: 10.1128/JB.187.15.5387-5396.2005. PubMed DOI PMC
Warner D.M., Shafer W.M., Jerse A.E. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol. Microbiol. 2008;70:462–478. doi: 10.1111/j.1365-2958.2008.06424.x. PubMed DOI PMC
Rinker S.D., Trombley M.P., Gu X., Fortney K.R., Bauer M.E. Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon. Infect. Immun. 2011;79:2324–2334. doi: 10.1128/IAI.01316-10. PubMed DOI PMC
Zähner D., Zhou X., Chancey S.T., Pohl J., Shafer W.M., Stephens D.S. Human antimicrobial peptide LL-37 induces MefE/Mel-mediated macrolide resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 2010;54:3516–3519. doi: 10.1128/AAC.01756-09. PubMed DOI PMC
Doshi R., Gutmann D.A.P., Khoo Y.S.K., Fagg L.A., Van Veen H.W. The choreography of multidrug export. Biochem. Soc. Trans. 2011;39:807–811. doi: 10.1042/BST0390807. PubMed DOI
Li M., Cha D.J., Lai Y., Villaruz A.E., Sturdevant D.E., Otto M. The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol. Microbiol. 2007;66:1136–1147. doi: 10.1111/j.1365-2958.2007.05986.x. PubMed DOI
Sperandio B., Regnault B., Guo J., Zhang Z., Stanley S.L., Sansonetti P.J., Pédron T. Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. J. Exp. Med. 2008;205:1121–1132. doi: 10.1084/jem.20071698. PubMed DOI PMC
Chakraborty K., Ghosh S., Koley H., Mukhopadhyay A.K., Ramamurthy T., Saha D.R., Mukhopadhyay D., Roychowdhury S., Hamabata T., Takeda Y., et al. Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human β-defensin 1 (HBD-1) expression in the intestinal epithelial cells. Cell. Microbiol. 2008;10:2520–2537. doi: 10.1111/j.1462-5822.2008.01227.x. PubMed DOI
Bader M.W., Sanowar S., Daley M.E., Schneider A.R., Cho U., Xu W., Klevit R.E., Le Moual H., Miller S.I. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell. 2005;122:461–472. doi: 10.1016/j.cell.2005.05.030. PubMed DOI
Shprung T., Wani N.A., Wilmes M., Mangoni M.L., Bitler A., Shimoni E., Sahl H.G., Shai Y. Opposing effects of PhoPQ and PmrAB on the properties of Salmonella enterica serovar Typhimurium: Implications on resistance to antimicrobial peptides. Biochemistry. 2021;60:2943–2955. doi: 10.1021/acs.biochem.1c00287. PubMed DOI PMC
Koprivnjak T., Peschel A. Bacterial resistance mechanisms against host defense peptides. Cell. Mol. Life Sci. 2011;68:2243–2254. doi: 10.1007/s00018-011-0716-4. PubMed DOI PMC
McPhee J.B., Lewenza S., Hancock R.E.W. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol. Microbiol. 2003;50:205–217. doi: 10.1046/j.1365-2958.2003.03673.x. PubMed DOI
Groisman E.A. The pleiotropic two-component regulatory system PhoP-PhoQ. J. Bacteriol. 2001;183:1835–1842. doi: 10.1128/JB.183.6.1835-1842.2001. PubMed DOI PMC
Martynowycz M.W., Rice A., Andreev K., Nobre T.M., Kuzmenko I., Wereszczynski J., Gidalevitz D. Salmonella membrane structural remodeling increases resistance to antimicrobial peptide LL-37. ACS Infect. Dis. 2019;5:1214–1222. doi: 10.1021/acsinfecdis.9b00066. PubMed DOI PMC
Vlieghe P., Lisowski V., Martinez J., Khrestchatisky M. Synthetic therapeutic peptides: Science and market. Drug Discov. Today. 2010;15:40–56. doi: 10.1016/j.drudis.2009.10.009. PubMed DOI
McGregor D.P. Discovering and improving novel peptide therapeutics. Curr. Opin. Pharmacol. 2008;8:616–619. doi: 10.1016/j.coph.2008.06.002. PubMed DOI
Guidance for Industry Chronic Cutaneous Ulcer and Burn Wounds—Developing Products for Treatment. [(accessed on 24 May 2024)]; Available online: https://www.fda.gov/files/drugs/published/Chronic-Cutaneous-Ulcer-and-Burn-Wounds----Developing-Products-for-Treatment.pdf. PubMed
Fry D.E. Antimicrobial Peptides. Surg. Infect. 2018;19:804–811. doi: 10.1089/sur.2018.194. PubMed DOI
Limoli D.H., Rockel A.B., Host K.M., Jha A., Kopp B.T., Hollis T., Wozniak D.J. Cationic antimicrobial peptides promote microbial mutagenesis and pathoadaptation in chronic infections. PLoS Pathog. 2014;10:e1004083. doi: 10.1371/journal.ppat.1004083. PubMed DOI PMC
Dilek F., Gultepe B., Ozkaya E., Yazici M., Gedik A.H., Cakir E. Beyond anti-microbial properties: The role of cathelicidin in allergic rhinitis. Allergol. Immunopathol. 2016;44:297–302. doi: 10.1016/j.aller.2015.07.006. PubMed DOI
Guryanova S.V., Ovchinnikova T.V. Immunomodulatory and allergenic properties of antimicrobial peptides. Int. J. Mol. Sci. 2022;23:2499. doi: 10.3390/ijms23052499. PubMed DOI PMC
Piktel E., Niemirowicz K., Wnorowska U., Wątek M., Wollny T., Głuszek K., Góźdź S., Levental I., Bucki R. The role of cathelicidin LL-37 in cancer development. Arch. Immunol. Ther. Exp. 2016;64:33–46. doi: 10.1007/s00005-015-0359-5. PubMed DOI PMC
Kiatsurayanon C., Peng G., Niyonsaba F. Opposing roles of antimicrobial peptides in skin cancers. Curr. Pharm. Des. 2021;28:248–258. doi: 10.2174/1381612827666211021163318. PubMed DOI
van Harten R.M., van Woudenbergh E., van Dijk A., Haagsman H.P. Cathelicidins: Immunomodulatory antimicrobials. Vaccines. 2018;6:63. doi: 10.3390/vaccines6030063. PubMed DOI PMC
Ebbensgaard A., Mordhorst H., Overgaard M.T., Aarestrup F.M., Hansen E.B. Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity. PLoS ONE. 2018;13:e0197742. doi: 10.1371/journal.pone.0197742. PubMed DOI PMC
FDA Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. [(accessed on 15 May 2024)]; Available online: https://www.fda.gov/drugs/human-drug-compounding/safety-risks-associated-certain-bulk-drug-substances-nominated-use-compounding.
FDA Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA’s Efforts to Foster Discovery and Development of New Tools to Fight Antimicrobial-Resistant Infections. [(accessed on 13 May 2024)]; Available online: https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-fdas-efforts-foster-discovery-and-development-new-tools.