Acanthamoeba is a ubiquitous genus of amoebae that can act as opportunistic parasites in both humans and animals, causing a variety of ocular, nervous and dermal pathologies. Despite advances in Acanthamoeba therapy, the management of patients with Acanthamoeba infections remains a challenge for health services. Therefore, there is a need to search for new active substances against Acanthamoebae. In the present study, we evaluated the amoebicidal activity of nitroxoline against the trophozoite and cyst stages of six different strains of Acanthamoeba. The strain A. griffini showed the lowest IC50 value in the trophozoite stage (0.69 ± 0.01 µM), while the strain A. castellanii L-10 showed the lowest IC50 value in the cyst stage (0.11 ± 0.03 µM). In addition, nitroxoline induced in treated trophozoites of A. culbertsoni features compatibles with apoptosis and autophagy pathways, including chromatin condensation, mitochondrial malfunction, oxidative stress, changes in cell permeability and the formation of autophagic vacuoles. Furthermore, proteomic analysis of the effect of nitroxoline on trophozoites revealed that this antibiotic induced the overexpression and the downregulation of proteins involved in the apoptotic process and in metabolic and biosynthesis pathways.

Centro de Investigación Biomédica en Red de Enfermedades Infecciosas Instituto de Salud Carlos 3 28220 Madrid Spain

Departamento de Obstetricia y Ginecología Pediatría Medicina Preventiva y Salud Pública Toxicología Medicina Legal y Forense y Parasitología Universidad de La Laguna 38203 San Cristóbal de La Laguna Spain

Department of Biology Working Group Parasitology and Infection Biology University Koblenz 56070 Koblenz Germany

Department of Microbiology and Hospital Hygiene Bundeswehr Central Hospital Koblenz 56072 Koblenz Germany

Department of Parasitology Faculty of Science Charles University BIOCEV 252 50 Vestec Czech Republic

Institute for Medical Microbiology Immunology and Hygiene University Hospital Cologne Faculty of Medicine University of Cologne 50935 Cologne Germany

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias Avda Astrofísico Fco Sánchez S N 38203 San Cristóbal de La Laguna Spain

Parasitology Lab Central Military Hospital Koblenz 56072 Koblenz Germany

Zobrazit více v PubMed

Scheid P.L. Encyclopedia of Parasitology. Springer; Berlin/Heidelberg, Germany: 2016. Free-Living Amoebae as Human Pathogens: (Genus) Acanthamoeba; pp. 1078–1080.

Siddiqui R., Khan N.A. Biology and Pathogenesis of Acanthamoeba. Parasit. Vectors. 2012;5:6. doi: 10.1186/1756-3305-5-6. PubMed DOI PMC

Lorenzo-Morales J., Khan N.A., Walochnik J. An Update on Acanthamoeba Keratitis: Diagnosis, Pathogenesis and Treatment. Parasite. 2015;22:10. doi: 10.1051/parasite/2015010. PubMed DOI PMC

Khan N.A. Acanthamoeba Invasion of the Central Nervous System. Int. J. Parasitol. 2007;37:131–138. doi: 10.1016/j.ijpara.2006.11.010. PubMed DOI

Kalra S.K., Sharma P., Shyam K., Tejan N., Ghoshal U. Acanthamoeba and Its Pathogenic Role in Granulomatous Amebic Encephalitis. Exp. Parasitol. 2020;208:107788. doi: 10.1016/j.exppara.2019.107788. PubMed DOI

Lee D.C., Fiester S.E., Madeline L.A., Fulcher J.W., Ward M.E., Schammel C.M.-G., Hakimi R.K. Acanthamoeba spp. and Balamuthia mandrillaris Leading to Fatal Granulomatous Amebic Encephalitis. Forensic Sci. Med. Pathol. 2020;16:171–176. doi: 10.1007/s12024-019-00202-6. PubMed DOI

Fanselow N., Sirajuddin N., Yin X.-T., Huang A.J.W., Stuart P.M. Acanthamoeba Keratitis, Pathology, Diagnosis and Treatment. Pathogens. 2021;10:323. doi: 10.3390/pathogens10030323. PubMed DOI PMC

Maycock N.J.R., Jayaswal R. Update on Acanthamoeba Keratitis: Diagnosis, Treatment, and Outcomes. Cornea. 2016;35:713–720. doi: 10.1097/ICO.0000000000000804. PubMed DOI

Diehl M.L.N., Paes J., Rott M.B. Genotype Distribution of Acanthamoeba in Keratitis: A Systematic Review. Parasitol. Res. 2021;120:3051–3063. doi: 10.1007/s00436-021-07261-1. PubMed DOI PMC

Steinberg J.P., Galindo R.L., Kraus E.S., Ghanem K.G. Disseminated Acanthamebiasis in a Renal Transplant Recipient with Osteomyelitis and Cutaneous Lesions: Case Report and Literature Review. Clin. Infect. Dis. 2002;35:e43–e49. doi: 10.1086/341973. PubMed DOI

Torno M.S., Babapour R., Gurevitch A., Witt M.D. Cutaneous Acanthamoebiasis in AIDS. J. Am. Acad. Dermatol. 2000;42:351–354. doi: 10.1016/S0190-9622(00)90110-5. PubMed DOI

Walia R., Montoya J.G., Visvesvera G.S., Booton G.C., Doyle R.L. A Case of Successful Treatment of Cutaneous Acanthamoeba Infection in a Lung Transplant Recipient. Transpl. Infect. Dis. 2007;9:51–54. doi: 10.1111/j.1399-3062.2006.00159.x. PubMed DOI

Saberi R., Fakhar M., Makhlough A., Sedighi O., Tabaripour R., Asfaram S., Latifi A., Espahbodi F., Sharifpour A. First Evidence for Colonizing of Acanthamoeba T4 Genotype in Urinary Tracts of Patients with Recurrent Urinary Tract Infections. Acta Parasitol. 2021;66:932–937. doi: 10.1007/s11686-021-00358-8. PubMed DOI

Guimaraes A.J., Gomes K.X., Cortines J.R., Peralta J.M., Peralta R.H.S. Acanthamoeba spp. as a Universal Host for Pathogenic Microorganisms: One Bridge from Environment to Host Virulence. Microbiol. Res. 2016;193:30–38. doi: 10.1016/j.micres.2016.08.001. PubMed DOI

Mungroo M.R., Siddiqui R., Khan N.A. War of the Microbial World: Acanthamoeba spp. Interactions with Microorganisms. Folia Microbiol. 2021;66:689–699. doi: 10.1007/s12223-021-00889-7. PubMed DOI PMC

Scheid P., Zöller L., Pressmar S., Richard G., Michel R. An Extraordinary Endocytobiont in Acanthamoeba sp. Isolated from a Patient with Keratitis. Parasitol. Res. 2008;102:945–950. doi: 10.1007/s00436-007-0858-3. PubMed DOI

Scheid P. Relevance of Free-Living Amoebae as Hosts for Phylogenetically Diverse Microorganisms. Parasitol. Res. 2014;113:2407–2414. doi: 10.1007/s00436-014-3932-7. PubMed DOI

Rayamajhee B., Subedi D., Peguda H.K., Willcox M.D., Henriquez F.L., Carnt N. A Systematic Review of Intracellular Microorganisms within Acanthamoeba to Understand Potential Impact for Infection. Pathogens. 2021;10:225. doi: 10.3390/pathogens10020225. PubMed DOI PMC

Taravaud A., Fechtali-Moute Z., Loiseau P.M., Pomel S. Drugs Used for the Treatment of Cerebral and Disseminated Infections Caused by Free-Living Amoebae. Clin. Transl. Sci. 2021;14:791–805. doi: 10.1111/cts.12955. PubMed DOI PMC

Anwar A., Khan N.A., Siddiqui R. Combating Acanthamoeba spp. Cysts: What Are the Options? Parasit. Vectors. 2018;11:26. doi: 10.1186/s13071-017-2572-z. PubMed DOI PMC

Wang Y., Jiang L., Zhao Y., Ju X., Wang L., Jin L., Fine R.D., Li M. Biological Characteristics and Pathogenicity of Acanthamoeba. Front. Microbiol. 2023;14:1147077. doi: 10.3389/fmicb.2023.1147077. PubMed DOI PMC

Wolf M.A., Thielman N.M., Kraft B.D. Treatment of Acanthamoeba Encephalitis. Am. J. Med. 2022;135:e20–e21. doi: 10.1016/j.amjmed.2021.08.009. PubMed DOI

Ahmed U., Anwar A., Ong S., Anwar A., Khan N.A. Applications of Medicinal Chemistry for Drug Discovery against Acanthamoeba Infections. Med. Res. Rev. 2022;42:462–512. doi: 10.1002/med.21851. PubMed DOI

Schor S., Einav S. Combating Intracellular Pathogens with Repurposed Host-Targeted Drugs. ACS Infect. Dis. 2018;4:88–92. doi: 10.1021/acsinfecdis.7b00268. PubMed DOI PMC

Supuran C.T. Antiprotozoal Drugs: Challenges and Opportunities. Expert. Opin. Ther. Pat. 2023;33:133–136. doi: 10.1080/13543776.2023.2201432. PubMed DOI

Naber K.G., Niggemann H., Stein G., Stein G. Review of the Literature and Individual Patients’ Data Meta-Analysis on Efficacy and Tolerance of Nitroxoline in the Treatment of Uncomplicated Urinary Tract Infections. BMC Infect. Dis. 2014;14:628. doi: 10.1186/s12879-014-0628-7. PubMed DOI PMC

Kranz J., Schmidt S., Lebert C., Schneidewind L., Mandraka F., Kunze M., Helbig S., Vahlensieck W., Naber K., Schmiemann G., et al. The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention. Urol. Int. 2018;100:271–278. doi: 10.1159/000487645. PubMed DOI

Wagenlehner F., Kresken M., Wohlfarth E., Bahrs C., Grabein B., Strohmaier W.L., Naber K.G. Therapie Der Zystitis Mit Nitroxolin—NitroxWin. Die Urol. 2023;62:1186–1192. doi: 10.1007/s00120-023-02167-5. PubMed DOI PMC

Lin W., Sun J., Sadahira T., Xu N., Wada K., Liu C., Araki M., Xu A., Watanabe M., Nasu Y., et al. Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-Resistant Urothelial Bladder Cancer. Int. J. Biol. Sci. 2021;17:3255–3267. doi: 10.7150/ijbs.63125. PubMed DOI PMC

Wykowski R., Fuentefria A.M., de Andrade S.F. Antimicrobial Activity of Clioquinol and Nitroxoline: A Scoping Review. Arch. Microbiol. 2022;204:535. doi: 10.1007/s00203-022-03122-2. PubMed DOI PMC

Laurie M.T., White C.V., Retallack H., Wu W., Moser M.S., Sakanari J.A., Ang K., Wilson C., Arkin M.R., DeRisi J.L. Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen Balamuthia mandrillaris. mBio. 2018;9:e02051-18. doi: 10.1128/mBio.02051-18. PubMed DOI PMC

Hoffmann A.M., Wolke M., Rybniker J., Plum G., Fuchs F. In Vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis. Front. Pharmacol. 2022;13:906097. doi: 10.3389/fphar.2022.906097. PubMed DOI PMC

Fuchs F., Hamprecht A. Susceptibility of Carbapenemase-Producing Enterobacterales (CPE) to Nitroxoline. J. Antimicrob. Chemother. 2019;74:2934–2937. doi: 10.1093/jac/dkz275. PubMed DOI

Fuchs F., Becerra-Aparicio F., Xanthopoulou K., Seifert H., Higgins P.G. In Vitro Activity of Nitroxoline against Carbapenem-Resistant Acinetobacter Baumannii Isolated from the Urinary Tract. J. Antimicrob. Chemother. 2022;77:1912–1915. doi: 10.1093/jac/dkac123. PubMed DOI

Abouelhassan Y., Yang Q., Yousaf H., Nguyen M.T., Rolfe M., Schultz G.S., Huigens R.W. Nitroxoline: A Broad-Spectrum Biofilm-Eradicating Agent against Pathogenic Bacteria. Int. J. Antimicrob. Agents. 2017;49:247–251. doi: 10.1016/j.ijantimicag.2016.10.017. PubMed DOI

Fuchs F., Hof H., Hofmann S., Kurzai O., Meis J.F., Hamprecht A. Antifungal Activity of Nitroxoline against Candida auris Isolates. Clin. Microbiol. Infect. 2021;27:1697.e7–1697.e10. doi: 10.1016/j.cmi.2021.06.035. PubMed DOI

Knez D., Brus B., Coquelle N., Sosič I., Šink R., Brazzolotto X., Mravljak J., Colletier J.-P., Gobec S. Structure-Based Development of Nitroxoline Derivatives as Potential Multifunctional Anti-Alzheimer Agents. Bioorganic Med. Chem. 2015;23:4442–4452. doi: 10.1016/j.bmc.2015.06.010. PubMed DOI

Ren L., Jiang M., Xue D., Wang H., Lu Z., Ding L., Xie H., Wang R., Luo W., Xu L., et al. Nitroxoline Suppresses Metastasis in Bladder Cancer via EGR1/CircNDRG1/MiR-520h/Smad7/EMT Signaling Pathway. Int. J. Biol. Sci. 2022;18:5207–5220. doi: 10.7150/ijbs.69373. PubMed DOI PMC

Zhang Q., Wang S., Yang D., Pan K., Li L., Yuan S. Preclinical Pharmacodynamic Evaluation of Antibiotic Nitroxoline for Anticancer Drug Repurposing. Oncol. Lett. 2016;11:3265–3272. doi: 10.3892/ol.2016.4380. PubMed DOI PMC

Lazovic J., Guo L., Nakashima J., Mirsadraei L., Yong W., Kim H.J., Ellingson B., Wu H., Pope W.B. Nitroxoline Induces Apoptosis and Slows Glioma Growth in Vivo. Neuro Oncol. 2015;17:53–62. doi: 10.1093/neuonc/nou139. PubMed DOI PMC

Bojkova D., Zöller N., Tietgen M., Steinhorst K., Bechtel M., Rothenburger T., Kandler J.D., Schneider J., Corman V.M., Ciesek S., et al. Repurposing of the Antibiotic Nitroxoline for the Treatment of Mpox. J. Med. Virol. 2023;95:e28652. doi: 10.1002/jmv.28652. PubMed DOI

Spottiswoode N., Pet D., Kim A., Gruenberg K., Shah M., Ramachandran A., Laurie M.T., Zia M., Fouassier C., Boutros C.L., et al. Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline. Emerg. Infect. Dis. 2023;29:197–201. doi: 10.3201/eid2901.221531. PubMed DOI PMC

Chao-Pellicer J., Arberas-Jiménez I., Fuchs F., Sifaoui I., Piñero J.E., Lorenzo-Morales J., Scheid P. Repurposing of Nitroxoline as an Alternative Primary Amoebic Meningoencephalitis Treatment. Antibiotics. 2023;12:1280. doi: 10.3390/antibiotics12081280. PubMed DOI PMC

González-Robles A., Salazar-Villatoro L., Omaña-Molina M., Reyes-Batlle M., Martín-Navarro C.M., Lorenzo-Morales J. Morphological Features and In Vitro Cytopathic Effect of Acanthamoeba griffini Trophozoites Isolated from a Clinical Case. J. Parasitol. Res. 2014;2014:256310. doi: 10.1155/2014/256310. PubMed DOI PMC

Omaña-Molina M., González-Robles A., Iliana Salazar-Villatoro L., Lorenzo-Morales J., Cristóbal-Ramos A.R., Hernández-Ramírez V.I., Talamás-Rohana P., Méndez Cruz A.R., Martínez-Palomo A. Reevaluating the Role of Acanthamoeba Proteases in Tissue Invasion: Observation of Cytopathogenic Mechanisms on MDCK Cell Monolayers and Hamster Corneal Cells. Biomed. Res. Int. 2013;2013:461329. doi: 10.1155/2013/461329. PubMed DOI PMC

Rodríguez-Expósito R.L., Nicolás-Hernández D.S., Sifaoui I., Cuadrado C., Salazar-Villatoro L., Reyes-Batlle M., Hernández-Daranas A., Omaña-Molina M., Fernández J.J., Díaz-Marrero A.R., et al. Gongolarones as Antiamoeboid Chemical Scaffold. Biomed. Pharmacother. 2023;158:114185. doi: 10.1016/j.biopha.2022.114185. PubMed DOI

Sifaoui I., Díaz-Rodríguez P., Rodríguez-Expósito R.L., Reyes-Batlle M., López-Arencibia A., Salazar Villatoro L., Castelan-Ramírez I., Omaña-Molina M., Oliva A., Piñero J.E., et al. Pitavastatin Loaded Nanoparticles: A Suitable Ophthalmic Treatment for Acanthamoeba Keratitis Inducing Cell Death and Autophagy in Acanthamoeba polyphaga. Eur. J. Pharm. Biopharm. 2022;180:11–22. doi: 10.1016/j.ejpb.2022.09.020. PubMed DOI

Arbon D., Ženíšková K., Šubrtová K., Mach J., Štursa J., Machado M., Zahedifard F., Leštinová T., Hierro-Yap C., Neuzil J., et al. Repurposing of MitoTam: Novel Anti-Cancer Drug Candidate Exhibits Potent Activity against Major Protozoan and Fungal Pathogens. Antimicrob. Agents Chemother. 2022;66:e0072722. doi: 10.1128/aac.00727-22. PubMed DOI PMC

Hughes C.S., Moggridge S., Müller T., Sorensen P.H., Morin G.B., Krijgsveld J. Single-Pot, Solid-Phase-Enhanced Sample Preparation for Proteomics Experiments. Nat. Protoc. 2019;14:68–85. doi: 10.1038/s41596-018-0082-x. PubMed DOI

Rappsilber J., Mann M., Ishihama Y. Protocol for Micro-Purification, Enrichment, Pre-Fractionation and Storage of Peptides for Proteomics Using StageTips. Nat. Protoc. 2007;2:1896–1906. doi: 10.1038/nprot.2007.261. PubMed DOI

Hebert A.S., Richards A.L., Bailey D.J., Ulbrich A., Coughlin E.E., Westphall M.S., Coon J.J. The One Hour Yeast Proteome. Mol. Cell. Proteom. 2014;13:339–347. doi: 10.1074/mcp.M113.034769. PubMed DOI PMC

Cox J., Mann M. MaxQuant Enables High Peptide Identification Rates, Individualized p.p.b.-Range Mass Accuracies and Proteome-Wide Protein Quantification. Nat. Biotechnol. 2008;26:1367–1372. doi: 10.1038/nbt.1511. PubMed DOI

Cox J., Hein M.Y., Luber C.A., Paron I., Nagaraj N., Mann M. Accurate Proteome-Wide Label-Free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ. Mol. Cell. Proteom. 2014;13:2513–2526. doi: 10.1074/mcp.M113.031591. PubMed DOI PMC

Tyanova S., Temu T., Sinitcyn P., Carlson A., Hein M.Y., Geiger T., Mann M., Cox J. The Perseus Computational Platform for Comprehensive Analysis of (Prote)Omics Data. Nat. Methods. 2016;13:731–740. doi: 10.1038/nmeth.3901. PubMed DOI

Baig A.M., Lalani S., Khan N.A. Apoptosis in Acanthamoeba castellanii Belonging to the T4 Genotype. J. Basic Microbiol. 2017;57:574–579. doi: 10.1002/jobm.201700025. PubMed DOI

Kaczanowski S., Sajid M., Reece S.E. Evolution of Apoptosis-like Programmed Cell Death in Unicellular Protozoan Parasites. Parasit. Vectors. 2011;4:44. doi: 10.1186/1756-3305-4-44. PubMed DOI PMC

Niemann A., Takatsuki A., Elsässer H.-P. The Lysosomotropic Agent Monodansylcadaverine Also Acts as a Solvent Polarity Probe. J. Histochem. Cytochem. 2000;48:251–258. doi: 10.1177/002215540004800210. PubMed DOI

Biederbick A., Kern H.F., Elsässer H.P. Monodansylcadaverine (MDC) Is a Specific in Vivo Marker for Autophagic Vacuoles. Eur. J. Cell Biol. 1995;66:3–14. PubMed

Zorova L.D., Popkov V.A., Plotnikov E.Y., Silachev D.N., Pevzner I.B., Jankauskas S.S., Babenko V.A., Zorov S.D., Balakireva A.V., Juhaszova M., et al. Mitochondrial Membrane Potential. Anal. Biochem. 2018;552:50–59. doi: 10.1016/j.ab.2017.07.009. PubMed DOI PMC

Wijma R.A., Huttner A., Koch B.C.P., Mouton J.W., Muller A.E. Review of the Pharmacokinetic Properties of Nitrofurantoin and Nitroxoline. J. Antimicrob. Chemother. 2018;73:2916–2926. doi: 10.1093/jac/dky255. PubMed DOI

Bergogne-Berezin E., Berthelot G., Muller-Serieys C. [Present Status of Nitroxoline] Pathol. Biol. 1987;35:873–878. PubMed

Mrhar A., Kopitar Z., Kozjek F., Presl V., Karba R. Clinical Pharmacokinetics of Nitroxoline. Int. J. Clin. Pharmacol. Biopharm. 1979;17:476–481. PubMed

Sharma G., Kalra S.K., Tejan N., Ghoshal U. Nanoparticles Based Therapeutic Efficacy against Acanthamoeba: Updates and Future Prospect. Exp. Parasitol. 2020;218:108008. doi: 10.1016/j.exppara.2020.108008. PubMed DOI

Varshosaz J., Fard M.M., Mirian M., Hassanzadeh F. Targeted Nanoparticles for Co-Delivery of 5-FU and Nitroxoline, a Cathepsin B Inhibitor, in HepG2 Cells of Hepatocellular Carcinoma. Anti-Cancer Agents Med. Chem. 2020;20:346–358. doi: 10.2174/1871520619666190930124746. PubMed DOI

Shim J.S., Matsui Y., Bhat S., Nacev B.A., Xu J., Bhang H.C., Dhara S., Han K.C., Chong C.R., Pomper M.G., et al. Effect of Nitroxoline on Angiogenesis and Growth of Human Bladder Cancer. JNCI J. Natl. Cancer Inst. 2010;102:1855–1873. doi: 10.1093/jnci/djq457. PubMed DOI PMC

Chang W.-L., Hsu L.-C., Leu W.-J., Chen C.-S., Guh J.-H. Repurposing of Nitroxoline as a Potential Anticancer Agent against Human Prostate Cancer—A Crucial Role on AMPK/MTOR Signaling Pathway and the Interplay with Chk2 Activation. Oncotarget. 2015;6:39806–39820. doi: 10.18632/oncotarget.5655. PubMed DOI PMC

Thomson S., Rice C.A., Zhang T., Edrada-Ebel R., Henriquez F.L., Roberts C.W. Characterisation of Sterol Biosynthesis and Validation of 14α-Demethylase as a Drug Target in Acanthamoeba. Sci. Rep. 2017;7:8247. doi: 10.1038/s41598-017-07495-z. PubMed DOI PMC

Sobke A., Makarewicz O., Baier M., Bär C., Pfister W., Gatermann S.G., Pletz M.W., Forstner C. Empirical Treatment of Lower Urinary Tract Infections in the Face of Spreading Multidrug Resistance: In Vitro Study on the Effectiveness of Nitroxoline. Int. J. Antimicrob. Agents. 2018;51:213–220. doi: 10.1016/j.ijantimicag.2017.10.010. PubMed DOI

Veschi S., Ronci M., Lanuti P., De Lellis L., Florio R., Bologna G., Scotti L., Carletti E., Brugnoli F., Di Bella M.C., et al. Integrative Proteomic and Functional Analyses Provide Novel Insights into the Action of the Repurposed Drug Candidate Nitroxoline in AsPC-1 Cells. Sci. Rep. 2020;10:2574. doi: 10.1038/s41598-020-59492-4. PubMed DOI PMC

Sobke A., Klinger M., Hermann B., Sachse S., Nietzsche S., Makarewicz O., Keller P.M., Pfister W., Straube E. The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas Aeruginosa Biofilms by Chelation of Iron and Zinc. Antimicrob. Agents Chemother. 2012;56:6021–6025. doi: 10.1128/AAC.01484-12. PubMed DOI PMC

Conte L., Zara V. The Rieske Iron-Sulfur Protein: Import and Assembly into the Cytochrome Complex of Yeast Mitochondria. Bioinorg. Chem. Appl. 2011;2011:363941. doi: 10.1155/2011/363941. PubMed DOI PMC

Kresken M., Körber-Irrgang B. In Vitro Activity of Nitroxoline against Escherichia coli Urine Isolates from Outpatient Departments in Germany. Antimicrob. Agents Chemother. 2014;58:7019–7020. doi: 10.1128/AAC.03946-14. PubMed DOI PMC

Hong Y., Kang J.-M., Joo S.-Y., Song S.-M., Lê H.G., Thái T.L., Lee J., Goo Y.-K., Chung D.-I., Sohn W.-M., et al. Molecular and Biochemical Properties of a Cysteine Protease of Acanthamoeba castellanii. Korean J. Parasitol. 2018;56:409–418. doi: 10.3347/kjp.2018.56.5.409. PubMed DOI PMC

Lee J.-Y., Song S.-M., Moon E.-K., Lee Y.-R., Jha B.K., Danne D.-B.S., Cha H.-J., Yu H.S., Kong H.-H., Chung D.-I., et al. Cysteine Protease Inhibitor (AcStefin) Is Required for Complete Cyst Formation of Acanthamoeba. Eukaryot. Cell. 2013;12:567–574. doi: 10.1128/EC.00308-12. PubMed DOI PMC

Tikhomirova T.S., Selivanova O.M., Galzitskaya O.V. α-Crystallins Are Small Heat Shock Proteins: Functional and Structural Properties. Biochemistry. 2017;82:106–121. doi: 10.1134/S0006297917020031. PubMed DOI

Yang G., Pan W., Zhang R., Pan Y., Guo Q., Song W., Zheng W., Nie X. Genome-Wide Identification and Characterization of Caffeoyl-Coenzyme A O-Methyltransferase Genes Related to the Fusarium Head Blight Response in Wheat. BMC Genom. 2021;22:504. doi: 10.1186/s12864-021-07849-y. PubMed DOI PMC

Lee H.-C., Wei Y.-H. Mitochondrial Biogenesis and Mitochondrial DNA Maintenance of Mammalian Cells under Oxidative Stress. Int. J. Biochem. Cell Biol. 2005;37:822–834. doi: 10.1016/j.biocel.2004.09.010. PubMed DOI

Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model

Amoebicidal Effect of COVID Box Molecules against Acanthamoeba: A Study of Cell Death