Many pathogens have evolved sophisticated strategies to evade autophagy, a crucial cellular defense mechanism that typically targets and degrades invading microorganisms. By subverting or inhibiting autophagy, these pathogens can create a more favorable environment for their replication and survival within the host. For instance, some bacteria secrete factors that block autophagosome formation, while others might escape from autophagosomes before degradation. These evasion tactics are critical for the pathogens' ability to establish and maintain infections. Understanding the mechanisms by which pathogens avoid autophagy is crucial for developing new therapeutic strategies, as enhancing autophagy could bolster the host's immune response and aid in the elimination of pathogenic bacteria. Francisella tularensis can manipulate host cell pathways to prevent its detection and destruction by autophagy, thereby enhancing its virulence. Given the potential for F. tularensis to be used as a bioterrorism agent due to its high infectivity and ability to cause severe disease, research into how this pathogen evades autophagy is of critical importance. By unraveling these mechanisms, new therapeutic approaches could be developed to enhance autophagic responses and strengthen host defense against this and other similarly evasive pathogens.

Department of Molecular Pathology and Biology Military Faculty of Medicine University of Defence Hradec Kralove Czechia

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czechia

Zobrazit více v PubMed

Abd El Maksoud A. I., Elebeedy D., Abass N. H., Awad A. M., Nasr G. M., Roshdy T., et al. . (2019). Methylomic changes of autophagy-related genes by legionella effector lpg2936 in infected macrophages. Front. Cell Dev. Biol. 7. doi: 10.3389/fcell.2019.00390 PubMed DOI PMC

Alam A., Golovliov I., Javed E., Sjöstedt A. (2018). ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication. Sci. Rep. 8, 11324. doi: 10.1038/s41598-018-29745-4 PubMed DOI PMC

Arasaki K., Mikami Y., Shames S. R., Inoue H., Wakana Y., Tagaya M. (2017). Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17. Nat. Commun. 8, 15406. doi: 10.1038/ncomms15406 PubMed DOI PMC

Ashida H., Mimuro H., Sasakawa C. (2015). Shigella manipulates host immune responses by delivering effector proteins with specific roles. Front. Immunol. 6. doi: 10.3389/fimmu.2015.00219 PubMed DOI PMC

Barel M., Charbit A. (2013). Francisella tularensis intracellular survival: To eat or to die. Microbes Infection. 989–997. doi: 10.1016/j.micinf.2013.09.009 PubMed DOI

Barnett T. C., Liebl D., Seymour L. M., Gillen C. M., Lim J. Y., LaRock C. N., et al. . (2013). The globally disseminated M1T1 clone of Group A Streptococcus evades autophagy for intracellular replication. Cell Host Microbe 14, 675–682. doi: 10.1016/j.chom.2013.11.003 PubMed DOI PMC

Baxt L. A., Goldberg M. B. (2014). Host and bacterial proteins that repress recruitment of LC3 to shigella early during infection. PLoS One 9, e94653. doi: 10.1371/journal.pone.0094653 PubMed DOI PMC

Beck W. H. J., Kim D., Das J., Yu H., Smolka M. B., Mao Y. (2020). Glucosylation by the legionella effector setA promotes the nuclear localization of the transcription factor TFEB. iScience 23, 101300. doi: 10.1016/j.isci.2020.101300 PubMed DOI PMC

Benjamin J. L., Sumpter R., Levine B., Hooper L. V. (2013). Intestinal epithelial autophagy is essential for host defense against invasive bacteria. Cell Host Microbe 13, 723–734. doi: 10.1016/j.chom.2013.05.004 PubMed DOI PMC

Bergmann R., Gulotta G., Andreoni F., Sumitomo T., Kawabata S., Zinkernagel A. S., et al. . (2022). The group A Streptococcus interleukin-8 protease SpyCEP promotes bacterial intracellular survival by evasion of autophagy. Infect. Microbes Dis. 4, 116–123. doi: 10.1097/im9.0000000000000098 PubMed DOI PMC

Bhogaraju S., Kalayil S., Liu Y., Bonn F., Colby T., Matic I., et al. . (2016). Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell 167, 1636–1649.e13. doi: 10.1016/j.cell.2016.11.019 PubMed DOI

Brodmann M., Schnider S. T., Basler M. (2021). Type VI secretion system and its effectors pdpC, pdpD, and opiA contribute to Francisella virulence in galleria mellonella larvae. Infection Immun. 89, e0057920. doi: 10.1128/iai.00579-20 PubMed DOI PMC

Bröms J. E., Sjöstedt A., Lavander M. (2010). The role of the Francisella tularensis pathogenicity island in type VI secretion, intracellular survival, and modulation of host cell signaling. Front. Microbiol. 1. doi: 10.3389/fmicb.2010.00136 PubMed DOI PMC

Case E. D. R., Chong A., Wehrly T. D., Hansen B., Child R., Hwang S., et al. . (2014). The rancisella O-antigen mediates survival in the macrophage cytosol via autophagy avoidance. Cell. Microbiol. 16, 862–877. doi: 10.1111/cmi.12246 PubMed DOI PMC

Castillo E. F., Dekonenko A., Arko-Mensah J., Mandell M. A., Dupont N., Jiang S., et al. . (2012). Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc. Natl. Acad. Sci. U. S. A. 109, E3168–E3176. doi: 10.1073/pnas.1210500109 PubMed DOI PMC

Celli J. (2019). The intracellular life cycle of brucella spp. Microbiol. Spectr. 7. doi: 10.1128/microbiolspec.bai-0006-2019 PubMed DOI PMC

Celli J., Zahrt T. C. (2013). Mechanisms of Francisella tularensis intracellular pathogenesis. Cold Spring Harbor Perspect. Med. 3, a010314. doi: 10.1101/cshperspect.a010314 PubMed DOI PMC

Chatterjee R., Chaudhuri D., Setty S. R. G., Chakravortty D. (2023). Deceiving the big eaters: Salmonella Typhimurium SopB subverts host cell xenophagy in macrophages via dual mechanisms. Microbes Infection 25, 105128. doi: 10.1016/j.micinf.2023.105128 PubMed DOI

Chaudhary A., Kamischke C., Leite M., Altura M. A., Kinman L., Kulasekara H., et al. . (2018). [amp]]beta;-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses. Sci. Signaling 11, eaat7493. doi: 10.1126/scisignal.aat7493 PubMed DOI

Chaudhuri R. R., Ren C.-P., Desmond L., Vincent G. A., Silman N. J., Brehm J. K., et al. . (2007). Genome sequencing shows that European isolates of Francisella tularensis subspecies tularensis are almost identical to US laboratory strain Schu S4. PLoS One 2, e352. doi: 10.1371/journal.pone.0000352 PubMed DOI PMC

Checroun C., Wehrly T. D., Fischer E. R., Hayes S. F., Celli J. (2006). Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication. Proc. Natl. Acad. Sci. U. S. A. 103, 14578–14583. doi: 10.1073/pnas.0601838103 PubMed DOI PMC

Chong A., Wehrly T. D., Child R., Hansen B., Hwang S., Virgin H. W., et al. . (2012). Cytosolic clearance of replication-deficient mutants reveals Francisella tularensis interactions with the autophagic pathway. Autophagy 8, 1342–1356. doi: 10.4161/auto.20808 PubMed DOI PMC

Choy A., Dancourt J., Mugo B., O’Connor T. J., Isberg R. R., Melia T. J., et al. . (2012). The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Sci. (New York N.Y.) 338, 1072–1076. doi: 10.1126/science.1227026 PubMed DOI PMC

Claude-Taupin A., Bissa B., Jia J., Gu Y., Deretic V. (2018). Role of autophagy in IL-1β export and release from cells. Semin. Cell Dev. Biol. 83, 36–41. doi: 10.1016/j.semcdb.2018.03.012 PubMed DOI PMC

Clemens D. L., Ge P., Lee B.-Y., Horwitz M. A., Zhou Z. H. (2015). Atomic structure of T6SS reveals interlaced array essential to function. Cell 160, 940–951. doi: 10.1016/j.cell.2015.02.005 PubMed DOI PMC

Clemens D. L., Lee B.-Y., Horwitz M. A. (2004). Virulent and avirulent strains of Francisella tularensis prevent acidification and maturation of their phagosomes and escape into the cytoplasm in human macrophages. Infection Immun. 72, 3204–3217. doi: 10.1128/IAI.72.6.3204-3217.2004 PubMed DOI PMC

Corkery D. P., Nadeem A., Aung K. M., Hassan A., Liu T., Cervantes-Rivera R., et al. . (2021). Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy. J. Cell Sci. 134, jcs252015. doi: 10.1242/jcs.252015 PubMed DOI

Cremer T. J., Amer A., Tridandapani S., Butchar J. P. (2009). Francisella tularensis regulates autophagy-related host cell signaling pathways. Autophagy 5, 125–128. doi: 10.4161/auto.5.1.7305 PubMed DOI PMC

Dall’Armi C., Devereaux K. A., Di Paolo G. (2013). The role of lipids in the control of autophagy. Curr. biology: CB 23, R33–R45. doi: 10.1016/j.cub.2012.10.041 PubMed DOI PMC

Degabriel M., Valeva S., Boisset S., Henry T. (2023). Pathogenicity and virulence of Francisella tularensis . Virulence 14, 2274638. doi: 10.1080/21505594.2023.2274638 PubMed DOI PMC

Degtyar E., Zusman T., Ehrlich M., Segal G. (2009). A Legionella effector acquired from protozoa is involved in sphingolipids metabolism and is targeted to the host cell mitochondria. Cell. Microbiol. 11, 1219–1235. doi: 10.1111/j.1462-5822.2009.01328.x PubMed DOI

De Leon J. A., Qiu J., Nicolai C. J., Counihan J. L., Barry K. C., Xu L., et al. . (2017). Positive and Negative Regulation of the Master Metabolic Regulator mTORC1 by Two Families of Legionella pneumophila Effectors. Cell Rep. 21, 2031–2038. doi: 10.1016/j.celrep.2017.10.088 PubMed DOI PMC

Deretic V., Saitoh T., Akira S. (2013). ‘Autophagy in infection, inflammation and immunity’, Nature Reviews. Immunology 13, 722–737. doi: 10.1038/nri3532 PubMed DOI PMC

Dortet L., Mostowy S., Samba-Louaka A., Gouin E., Nahori M.-A., Wiemer E. A. C., et al. . (2011). Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy. PLoS Pathog. 7, e1002168. doi: 10.1371/journal.ppat.1002168 PubMed DOI PMC

Dortet L., Mostowy S., Cossart P. (2012). Listeria and autophagy escape. Autophagy. 132–134. doi: 10.4161/auto.8.1.18218 PubMed DOI PMC

Eshraghi A., et al. . (2016). Secreted effectors encoded within and outside of the Francisella pathogenicity island promote intramacrophage growth. Cell Host Microbe 20, 573–583. doi: 10.1016/j.chom.2016.10.008 PubMed DOI PMC

Faron M., Fletcher J. R., Rasmussen J. A., Long M. E., Allen L.-A. H., Jones B. D. (2013). The Francisella tularensis migR, trmE, and cphA genes contribute to F. tularensis pathogenicity island gene regulation and intracellular growth by modulation of the stress alarmone ppGpp. Infection Immun. 81, 2800–2811. doi: 10.1128/IAI.00073-13 PubMed DOI PMC

Feng Z.-Z., Jiang A.-J., Mao A.-W., Feng Y., Wang W., Li J., et al. . (2018). The Salmonella effectors SseF and SseG inhibit Rab1A-mediated autophagy to facilitate intracellular bacterial survival and replication. J. Biol. Chem. 293, 9662–9673. doi: 10.1074/jbc.M117.811737 PubMed DOI PMC

Ganesan R., Hos N. J., Gutierrez S., Fischer J., Stepek J. M., Daglidu E., et al. . (2017). Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy. PLoS Pathog. 13, e1006227. doi: 10.1371/journal.ppat.1006227 PubMed DOI PMC

Ge P., Lei Z., Yu Y., Lu Z., Qiang L., Chai Q., et al. . (2022). M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival. Autophagy 18, 576–594. doi: 10.1080/15548627.2021.1938912 PubMed DOI PMC

Gradowski M., Pawłowski K. (2017). The Legionella pneumophila effector Lpg1137 is a homologue of mitochondrial SLC25 carrier proteins, not of known serine proteases. PeerJ 5, e3849. doi: 10.7717/peerj.3849 PubMed DOI PMC

Gutierrez M. G., Saka H. A., Chinen I., Zoppino F. C.M., Yoshimori T., Bocco J. L., et al. . (2007). Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae. Proc. Natl. Acad. Sci. USA 104, 1829. doi: 10.1073/pnas.0601437104 PubMed DOI PMC

Hamasaki M., Furuta N., Matsuda A., Nezu A., Yamamoto A., Fujita N., et al. . (2013). Autophagosomes form at ER-mitochondria contact sites. Nature 495, 389–393. doi: 10.1038/nature11910 PubMed DOI

Harris J., Hartman M., Roche C., Zeng S. G., O’Shea A., Sharp F. A., et al. . (2011). Autophagy controls IL-1β Secretion by targeting pro-IL-1β for degradation. J. Biol. Chem. 286, 9587–9597. doi: 10.1074/jbc.M110.202911 PubMed DOI PMC

Härtlova A., Link M., Balounova J., Benesova M., Resch U., Straskova A., et al. . (2014). Quantitative proteomics analysis of macrophage-derived lipid rafts reveals induction of autophagy pathway at the early time of francisella tularensis LVS infection. J. Proteome Res. 13, 796–804. doi: 10.1021/pr4008656 PubMed DOI

Hauser A. R. (2009). The type III secretion system of pseudomonas aeruginosa: infection by injection. Nature reviews. Microbiology 7, 654–665. doi: 10.1038/nrmicro2199 PubMed DOI PMC

Hernandez L. D., Pypaert M., Flavell R. A., Galán J. E. (2003). A Salmonella protein causes macrophage cell death by inducing autophagy. J. Cell Biol. 163, 1123–1131. doi: 10.1083/jcb.200309161 PubMed DOI PMC

Huang J., Brumell J. H. (2014). Bacteria–autophagy interplay: a battle for survival. Nat. Rev. Microbiol. 12, 101–114. doi: 10.1038/nrmicro3160 PubMed DOI PMC

Iula L., Keitelman I. A., Sabbione F., Fuentes F., Guzman M., Galletti J. G., et al. . (2018). Autophagy mediates interleukin-1β Secretion in human neutrophils. Front. Immunol. 9. doi: 10.3389/fimmu.2018.00269 PubMed DOI PMC

Jia X., Knyazeva A., Zhang Y., Castro-Gonzalez S., Nakamura S., Carlson L.-A., et al. . (2022). V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy. J. Cell Biol. 221, e202206040. doi: 10.1083/jcb.202206040 PubMed DOI PMC

Kaushik S., Cuervo A. M. (2018). The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol. 19, 365–381. doi: 10.1038/s41580-018-0001-6 PubMed DOI PMC

Kelava I., Mihelčić M., Ožanič M., Marečić V., Knežević M., Ćurlin M., et al. . (2020). Atg5-deficient mice infected with Francisella tularensis LVS demonstrate increased survival and less severe pathology in internal organs. Microorganisms 8, 1531. doi: 10.3390/microorganisms8101531 PubMed DOI PMC

Khweek A. A., Caution K., Akhter A., Abdulrahman B. A., Tazi M., Hassan H., et al. . (2013). A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy. Eur. J. Immunol. 43, 1333–1344. doi: 10.1002/eji.201242835 PubMed DOI PMC

Kim J., Kundu M., Viollet B., Guan K.-L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132–141. doi: 10.1038/ncb2152 PubMed DOI PMC

Kim J. K., Silwal P., Jo E.-K. (2020). Host-pathogen dialogues in autophagy, apoptosis, and necrosis during mycobacterial infection. Immune Network 20, e37. doi: 10.4110/in.2020.20.e37 PubMed DOI PMC

Klare I., Werner G., Witte W. (2001). Enterococci. Habitats, infections, virulence factors, resistances to antibiotics, transfer of resistance determinants. Contributions to Microbiol. 8, 108–122. doi: 10.1159/000060406 PubMed DOI

Konecna K., Hernychova L., Reichelova M., Lenco J., Klimentova J., Stulik J., et al. . (2010). Comparative proteomic profiling of culture filtrate proteins of less and highly virulent Francisella tularensis strains. Proteomics 10, 4501–4511. doi: 10.1002/pmic.201000248 PubMed DOI

Kumar S., Gu Y., Abudu Y. P., Bruun J.-A., Jain A., Farzam F., et al. . (2019). Phosphorylation of syntaxin 17 by TBK1 controls autophagy initiation. Dev. Cell 49, 130–144.e6. doi: 10.1016/j.devcel.2019.01.027 PubMed DOI PMC

Lauriano C. M., Barker J. R., Yoon S.-S., Nano F. E., Arulanandam B. P., Hassett D. J., et al. . (2004). MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival. Proc. Natl. Acad. Sci. U. S. A. 101, 4246–4249. doi: 10.1073/pnas.0307690101 PubMed DOI PMC

Ledvina H. E., Kelly K. A., Eshraghi A., Plemel R. L., Peterson S. B., Lee B., et al. . (2018). A phosphatidylinositol 3-kinase effector alters phagosomal maturation to promote intracellular growth of Francisella . Cell Host Microbe 24, 285–295.e8. doi: 10.1016/j.chom.2018.07.003 PubMed DOI PMC

Lemarignier M., Pizarro-Cerdá J. (2020). Autophagy and intracellular membrane trafficking subversion by pathogenic yersinia species. Biomolecules 10, 1637. doi: 10.3390/biom10121637 PubMed DOI PMC

Levine B., Kroemer G. (2019). Biological functions of autophagy genes: A disease perspective. Cell 176, 11–42. doi: 10.1016/j.cell.2018.09.048 PubMed DOI PMC

Li J., Qi L., Diao Z., Zhang M., Li B., Zhai Y., et al. . (2022). Brucella btpB manipulates apoptosis and autophagic flux in RAW264.7 cells. Int. J. Mol. Sci. 23, 14439. doi: 10.3390/ijms232214439 PubMed DOI PMC

Ligeon L.-A., Moreau K., Barois N., Bongiovanni A., Lacorre D.-A., Werkmeister E., et al. . (2014). Role of VAMP3 and VAMP7 in the commitment of Yersinia pseudotuberculosis to LC3-associated pathways involving single- or double-membrane vacuoles. Autophagy 10, 1588–1602. doi: 10.4161/auto.29411 PubMed DOI PMC

Lin D., Gao Y., Zhao L., Chen Y., An S., Peng Z. (2018). Enterococcus faecalis lipoteichoic acid regulates macrophages autophagy via PI3K/Akt/mTOR pathway. Biochem. Biophys. Res. Commun. 498, 1028–1036. doi: 10.1016/j.bbrc.2018.03.109 PubMed DOI

Louche A., Blanco A., Lacerda T. L.S., Cancade-Veyre L., Lionnet C., Bergé C., et al. . (2023). Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins. Nat. Commun. 14, 102. doi: 10.1038/s41467-022-35763-8 PubMed DOI PMC

Ludu J. S., de Bruin O. M., Duplantis B. N., Schmerk C. L., Chou A. Y., Elkins K. L., et al. . (2008). The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system. J. Bacteriology 190, 4584–4595. doi: 10.1128/JB.00198-08 PubMed DOI PMC

Mao K., Klionsky D. J. (2016). Xenophagy: A battlefield between host and microbe, and a possible avenue for cancer treatment. Autophagy 13, 223–224. doi: 10.1080/15548627.2016.1267075 PubMed DOI PMC

Maurin M. (2020). Francisella tularensis, tularemia and serological diagnosis. Front. Cell. Infection Microbiol. 10. doi: 10.3389/fcimb.2020.512090 PubMed DOI PMC

Mesquita F. S., Thomas M., Sachse M., Santos A. J. M., Figueira R., Holden D. W. (2012). The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS Pathog. 8, e1002743. doi: 10.1371/journal.ppat.1002743 PubMed DOI PMC

Mitchell G., Ge L., Huang Q., Chen C., Kianian S., Roberts M. F., et al. . (2015). Avoidance of autophagy mediated by PlcA or ActA is required for Listeria monocytogenes growth in macrophages. Infection Immun. 83, 2175–2184. doi: 10.1128/IAI.00110-15 PubMed DOI PMC

Mitchell G., Cheng M. I., Chen C., Nguyen B. N., Whiteley A. T., Kianian S., et al. . (2018). Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy. Proc. Natl. Acad. Sci. USA 115, E210–E217. doi: 10.1073/pnas.1716055115 PubMed DOI PMC

Moreau K., Lacas-Gervais S., Fujita N., Sebbane F., Yoshimori T., Simonet M., et al. . (2010). Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages. Cell. Microbiol. 12, 1108–1123. doi: 10.1111/j.1462-5822.2010.01456.x PubMed DOI

Nelson C. A., Murua C., Jones J. M., Mohler K., Zhang Y., Wiggins L., et al. . (2019). Francisella tularensis transmission by solid organ transplantation 20171. Emerging Infect. Dis. 25, 767–775. doi: 10.3201/eid2504.181807 PubMed DOI PMC

Omotade T. O., Roy C. R. (2020). Legionella pneumophila excludes autophagy adaptors from the ubiquitin-labeled vacuole in which it resides. Infection Immun. 88, e00793–e00719. doi: 10.1128/IAI.00793-19 PubMed DOI PMC

Orenstein S. J., Cuervo A. M. (2010). Chaperone-mediated autophagy: Molecular mechanisms and physiological relevance. Semin. Cell Dev. Biol. 21, 719–726. doi: 10.1016/j.semcdb.2010.02.005 PubMed DOI PMC

Ozanic M., Marecic V., Lindgren M., Sjöstedt A., Santic M. (2016). Phenotypic characterization of the Francisella tularensis ΔpdpC and ΔiglG mutants. Microbes Infection 18, 768–776. doi: 10.1016/j.micinf.2016.07.006 PubMed DOI

Pavlik P., Spidlova P. (2022). Arginine 58 is indispensable for proper function of the Francisella tularensis subsp. holarctica FSC200 HU protein, and its substitution alters virulence and mediates immunity against wild-type strain. Virulence. 13, 1790–1809. doi: 10.1080/21505594.2022.2132729 PubMed DOI PMC

Pechous R. D., McCarthy T. R., Zahrt T. C. (2009). Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development. Microbiol. Mol. Biol. reviews: MMBR 73, 684–711. doi: 10.1128/MMBR.00028-09 PubMed DOI PMC

Phalipon A., Sansonetti P. J. (2007). Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival? Immunol. Cell Biol. 85, 119–129. doi: 10.1038/sj.icb7100025 PubMed DOI

Pinotsis N., Waksman G. (2017). Crystal structure of the Legionella pneumophila Lpg2936 in complex with the cofactor S-adenosyl-L-methionine reveals novel insights into the mechanism of RsmE family methyltransferases. Protein Science: A Publ. Protein Soc. 26, 2381–2391. doi: 10.1002/pro.3305 PubMed DOI PMC

Price C., Jones S., Mihelcic M., Santic M., Abu Kwaik Y. (2020). Paradoxical pro-inflammatory responses by human macrophages to an amoebae host-adapted legionella effector. Cell Host Microbe 27, 571–584.e7. doi: 10.1016/j.chom.2020.03.003 PubMed DOI PMC

Pujol C., Klein K. A., Romanov G. A., Palmer L. E., Cirota C., Zhao Z., et al. . (2009). Yersinia pestis can reside in autophagosomes and avoid xenophagy in murine macrophages by preventing vacuole acidification. Infection Immun. 77, 2251–2261. doi: 10.1128/IAI.00068-09 PubMed DOI PMC

Qi X., Man S. M., Malireddi R. K.S., Karki R., Lupfer C., Gurung P., et al. . (2016). Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. J. Exp. Med. 213, 2081–2097. doi: 10.1084/jem.20151938 PubMed DOI PMC

Ramakrishnan G. (2017). Iron and virulence in Francisella tularensis . Front. Cell. Infection Microbiol. 7. doi: 10.3389/fcimb.2017.00107 PubMed DOI PMC

Rao L., De La Rosa I., Xu Y., Sha Y., Bhattacharya A., Holtzman M. J., et al. . (2021). Pseudomonas aeruginosa survives in epithelia by ExoS-mediated inhibition of autophagy and mTOR. EMBO Rep. 22, e50613. doi: 10.15252/embr.202050613 PubMed DOI PMC

Rigard M., Bröms J. E., Mosnier A., Hologne M., Martin A., Lindgren L., et al. . (2016). Francisella tularensis iglG belongs to a novel family of PAAR-like T6SS proteins and harbors a unique N-terminal extension required for virulence. PLoS Pathog. 12, e1005821. doi: 10.1371/journal.ppat.1005821 PubMed DOI PMC

Rolando M., Escoll P., Nora T., Botti J., Boitez V., Bedia C., et al. . (2016). Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. Proc. Natl. Acad. Sci. U. S. A. 113, 1901–1906. doi: 10.1073/pnas.1522067113 PubMed DOI PMC

Rowe H. M., Huntley J. F. (2015). From the outside-in: the Francisella tularensis envelope and virulence. Front. Cell. Infection Microbiol. 5. doi: 10.3389/fcimb.2015.00094 PubMed DOI PMC

Santic M., Molmeret M., Klose K. E., Jones S., Kwaik Y. A. (2005). The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm. Cell. Microbiol. 7, 969–979. doi: 10.1111/j.1462-5822.2005.00526.x PubMed DOI

Schmid D., Pypaert M., Münz C. (2007). Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26, 79–92. doi: 10.1016/j.immuni.2006.10.018 PubMed DOI PMC

Schnupf P., Portnoy D. A. (2007). isteriolysin O: a phagosome-specific lysin. Microbes Infection 9, 1176–1187. doi: 10.1016/j.micinf.2007.05.005 PubMed DOI

Seabaugh J. A., Anderson D. M. (2024). Pathogenicity and virulence of yersinia. Virulence 15, 2316439. doi: 10.1080/21505594.2024.2316439 PubMed DOI PMC

Shahnazari S., Namolovan A., Mogridge J., Kim P. K., Brumell J. H. (2011). Bacterial toxins can inhibit host cell autophagy through cAMP generation. Autophagy 7, 957–965. doi: 10.4161/auto.7.9.16435 PubMed DOI

Singh P., Subbian S. (2018). Harnessing the mTOR pathway for tuberculosis treatment. Front. Microbiol. 9. doi: 10.3389/fmicb.2018.00070 PubMed DOI PMC

Smith G. A., Marquis H., Jones S., Johnston N. C., Portnoy D. A., Goldfine H. (1995). The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infection Immun. 63, 4231–4237. doi: 10.1128/iai.63.11.4231-4237.1995 PubMed DOI PMC

Spidlova P., Stojkova P., Dankova V., Senitkova I., Santic M., Pinkas D., et al. . (2018). Francisella tularensis D-ala D-ala carboxypeptidase dacD is involved in intracellular replication and it is necessary for bacterial cell wall integrity. Front. Cell. Infection Microbiol. 8. doi: 10.3389/fcimb.2018.00111 PubMed DOI PMC

Spidlova P., Stojkova P., Sjöstedt A., Stulik J. (2020). Control of Francisella tularensis Virulence at Gene Level: Network of Transcription Factors. Microorganisms 8, 1622. doi: 10.3390/microorganisms8101622 PubMed DOI PMC

Spidlova P., Stulik J. (2017). Francisella tularensis type VI secretion system comes of age. Virulence 8, 628–631. doi: 10.1080/21505594.2016.1278336 PubMed DOI PMC

Starr T., Ng T. W., Wehrly T. D., Knodler L. A., Celli J. (2008). Brucella intracellular replication requires trafficking through the late endosomal/lysosomal compartment. Traffic (Copenhagen Denmark) 9, 678–694. doi: 10.1111/j.1600-0854.2008.00718.x PubMed DOI

Steele S., Brunton J., Ziehr B., Taft-Benz S., Moorman N., Kawula T. (2013). Francisella tularensis Harvests Nutrients Derived via ATG5-Independent Autophagy to Support Intracellular Growth. PLoS Pathog. 9, e1003562. doi: 10.1371/journal.ppat.1003562 PubMed DOI PMC

Stojkova P., Spidlova P., Lenco J., Rehulkova H., Kratka L., Stulik J. (2018). HU protein is involved in intracellular growth and full virulence of Francisella tularensis . Virulence 9, 754–770. doi: 10.1080/21505594.2018.1441588 PubMed DOI PMC

Stojkova P., Spidlova P. (2022). Bacterial nucleoid-associated protein HU as an extracellular player in host-pathogen interaction. Front. Cell. Infection Microbiol. 12. doi: 10.3389/fcimb.2022.999737 PubMed DOI PMC

Stojkova P., Spidlova P., Stulik J. (2019). Nucleoid-associated protein HU: A lilliputian in gene regulation of bacterial virulence. Front. Cell. Infection Microbiol. 9. doi: 10.3389/fcimb.2019.00159 PubMed DOI PMC

Strong E. J., Ng T. W., Porcelli S. A., Lee S. (2021). Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 proteins inhibit autophagy by interaction with rab1A. mSphere 6, e0054921. doi: 10.1128/msphere.00549-21. PubMed DOI PMC

Tan T., Lee W. L., Alexander D. C., Grinstein S., Liu J. (2006). The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation. Cell. Microbiol. 8, 1417–1429. doi: 10.1111/j.1462-5822.2006.00721.x PubMed DOI

Tattoli I., Sorbara M. T., Vuckovic D., Ling A., Soares F., Carneiro L. A. M., et al. . (2012). Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11, 563–575. doi: 10.1016/j.chom.2012.04.012 PubMed DOI

Thomas D. R., Newton P., Lau N., Newton H. J. (2020). Interfering with Autophagy: The opposing strategies deployed by legionella pneumophila and coxiella burnetii effector proteins. Front. Cell. Infection Microbiol. 10. doi: 10.3389/fcimb.2020.599762 PubMed DOI PMC

Torres A., Luke J. D., Kullas A. L., Kapilashrami K., Botbol Y., Koller A., et al. . (2016). Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming. J. Leukocyte Biol. 99, 387–398. doi: 10.1189/jlb.4A0615-252R PubMed DOI PMC

Travis B. A., Ramsey K. M., Prezioso S. M., Tallo T., Wandzilak J. M., Hsu A., et al. . (2021). Structural basis for virulence activation of francisella tularensis . Mol. Cell 81, 139–152.e10. doi: 10.1016/j.molcel.2020.10.035 PubMed DOI PMC

Uda A., Sharma N., Takimoto K., Deyu T., Koyama Y., Park E., et al. . (2016). Pullulanase is necessary for the efficient intracellular growth of Francisella tularensis . PLoS One 11, e0159740. doi: 10.1371/journal.pone.0159740 PubMed DOI PMC

Valencia Lopez M. J., Schimmeck H., Gropengießer J., Middendorf L., Quitmann M., Schneider C., et al. . (2019). Activation of the macroautophagy pathway by Yersinia enterocolitica promotes intracellular multiplication and egress of yersiniae from epithelial cells. Cell. Microbiol. 21, e13046. doi: 10.1111/cmi.13046 PubMed DOI

Van Kaer L., Parekh V. V., Postoak J. L., Wu L. (2019). Role of autophagy in MHC class I-restricted antigen presentation. Mol. Immunol. 113, 2–5. doi: 10.1016/j.molimm.2017.10.021 PubMed DOI PMC

Vozandychova V., Stojkova P., Hercik K., Rehulka P., Stulik J. (2021). The ubiquitination system within bacterial host–pathogen interactions. Microorganisms 9, 638. doi: 10.3390/microorganisms9030638 PubMed DOI PMC

Vozandychova V., Rehulka P., Hercik K., Spidlova P., Pavlik P., Hanus J., et al. . (2023). Modified activities of macrophages’ deubiquitinating enzymes after Francisella infection. Front. Immunol. 14. doi: 10.3389/fimmu.2023.1252827 PubMed DOI PMC

Williams K., Gokulan K., Shelman D., Akiyama T., Khan A., Khare S. (2015). Cytotoxic mechanism of cytolethal distending toxin in nontyphoidal Salmonella serovar (Salmonella Javiana) during macrophage infection. DNA Cell Biol. 34, 113–124. doi: 10.1089/dna.2014.2602 PubMed DOI

Wong D., Bach H., Sun J., Hmama Z., Av-Gay Y. (2011). Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+–ATPase to inhibit phagosome acidification. Proc. Natl. Acad. Sci. U. S. A. 108, 19371–19376. doi: 10.1073/pnas.1109201108 PubMed DOI PMC

Wrench A. P., Gardner C. L., Siegel S. D., Pagliai F. A., Malekiha M., Gonzalez C. F., et al. . (2013). MglA/sspA complex interactions are modulated by inorganic polyphosphate. PLoS One 8, e76428. doi: 10.1371/journal.pone.0076428 PubMed DOI PMC

Wu S., Shen Y., Zhang S., Xiao Y., Shi S. (2020). Salmonella interacts with autophagy to offense or defense. Front. Microbiol. 11. doi: 10.3389/fmicb.2020.00721 PubMed DOI PMC

Yamamoto H., Matsui T. (2024). Molecular mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. J. Nippon Med. School = Nippon Ika Daigaku Zasshi 91, 2–9. doi: 10.1272/jnms.JNMS.2024_91-102 PubMed DOI

Yoshikawa Y., Ogawa M., Hain T., Chakraborty T., Sasakawa C. (2009. a). Listeria monocytogenes ActA is a key player in evading autophagic recognition. Autophagy 5, 1220–1221. doi: 10.4161/auto.5.8.10177 PubMed DOI

Yoshikawa Y., Ogawa M., Hain T., Yoshida M., Fukumatsu M., Kim M., et al. . (2009. b). Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat. Cell Biol. 11, 1233–1240. doi: 10.1038/ncb1967 PubMed DOI

Yuan K., Huang C., Fox J., Laturnus D., Carlson E., Zhang B., et al. . (2012). Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages. J. Cell Sci. 125, 507–515. doi: 10.1242/jcs.094573 PubMed DOI PMC

Yuk J.-M., Yoshimori T., Jo E.-K. (2012). Autophagy and bacterial infectious diseases. Exp. Mol. Med. 44, 99–108. doi: 10.3858/emm.2012.44.2.032 PubMed DOI PMC

Zhang W., Dong C., Xiong S. (2024). Mycobacterial SapM hampers host autophagy initiation for intracellular bacillary survival via dephosphorylating Raptor. iScience 27, 109671. doi: 10.1016/j.isci.2024.109671 PubMed DOI PMC

Zheng Y. T., Shahnazari S., Brech A., Lamark T., Johansen T., Brumell J. H. (2009). The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J. Immunol. (Baltimore Md.: 1950) 183, 5909–5916. doi: 10.4049/jimmunol.0900441 PubMed DOI

Zou J., Shankar N. (2014). Enterococcus faecalis infection activates phosphatidylinositol 3-kinase signaling to block apoptotic cell death in macrophages. Infection Immun. 82, 5132–5142. doi: 10.1128/iai.02426-14 PubMed DOI PMC

Zou J., Shankar N. (2016). The opportunistic pathogen resists phagosome acidification and autophagy to promote intracellular survival in macrophages. Cell. Microbiol. 18, 831–843. doi: 10.1111/cmi.12556 PubMed DOI