Abstract
Bacterial infections caused by pathogenic bacteria, like tuberculosis by Mycobacterium tuberculosis, listeriosis by Listeria monocytogenes, and gastroenteritis by Salmonella typhimurium, are on the rise. With the increase in pathogen resistance to antibiotics, novel approaches are required for therapeutic interventions to treat bacterial infections. Autophagy is an essential host defense mechanism against infections and, in recent times, has shown promising potential as a therapeutic target in this regard. This article reviews the role of autophagy during infection with pathogenic bacteria and recent studies which highlight the importance of autophagy as a prospective therapeutic target.
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References
Anand PK, Tait SW, Lamkanfi M, Amer AO, Nunez G, Pagès G, Pouysségur J et al (2011) TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J Biol Chem 286:42981–42991
Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962
Birmingham CL, Smith AC, Bakowski MA, Yoshimori T, Brumell JH (2006) Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 281:11374–11383
Birmingham CL, Canadien V, Gouin E, Troy EB, Yoshimori T, Cossart P, Higgins DE, Brumell JH (2007) Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy 3:442–451
Birmingham CL, Canadien V, Kaniuk NA, Steinberg BE, Higgins DE, Brumell JH (2008) Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature 451:350–354
Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171:603–614
Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK et al (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456:259–263
Cemma M, Kim PK, Brumell JH (2011) The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway. Autophagy 7:341–345
Chandra V, Bhagyaraj E, Nanduri R, Ahuja N, Gupta P (2015) NR1D1 ameliorates Mycobacterium tuberculosis clearance through regulation of autophagy. Autophagy 11:1987–1997
Chen Z, Wang T, Liu Z, Zhang G, Wang J, Feng S et al (2015) Inhibition of autophagy by miR-30A induced by Mycobacteria tuberculosis as a possible mechanism of immune escape in human macrophages. Jpn J Infect Dis 68:420–424
Conway KL, Kuballa P, Songh JH, Patel KK, Castoreno AB, Yilmaz OH et al (2013) Atg16l1 is required for autophagy in intestinal epithelial cells and protection of mice from Salmonella infection. Gastroenterology 145:1347–1357
Dortet L, Mostowy S, Samba-Louaka A, Gouin E, Nahori MA, Wiemer EA, Dussurget O, Cossart P (2011) Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy. PLoS Pathog 7:e1002168
Duan L, Yi M, Chen J, Li S, Chen W (2016) Mycobacterium tuberculosis EIS gene inhibits macrophage autophagy through up-regulation of IL-10 by increasing the acetylation of histone H3. Biochem Biophys Res Commun 473:1229–1234
Dupont N, Lacas-Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, van der Goot FG, Sansonetti PJ, Lafont F (2009) Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe 6:137–149
Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T (2008) The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 19:2092–2100
Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221:3–12
Gluschko A, Herb M, Wiegmann K, Krut O, Neiss WF, Utermohlen O et al (2018) The β2 integrin Mac-1 induces protective LC3-associated phagocytosis of Listeria monocytogenes. Cell Host Microbe 23:324–337
Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211
Hanada T, Noda NN, Satomi Y et al (2007) The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282:37298–37302
Huang D, Bao L (2016) Mycobacterium tuberculosis EspB protein suppresses interferon-γ-induced autophagy in murine macrophages. J Microbiol Immunol Infect 49:859–865
Jamwal SV, Mehrotra P, Singh A, Siddiqui Z, Basu A, Raoy KV (2016) Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism. Sci Rep 6:23089. https://doi.org/10.1038/srep23089
Khweek AA, Caution K, Akhter A, Abdulrahman BA, Tazi M, Hassan H, Majumdar N et al (2013) A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy. Eur J Immunol 43:1333–1344
Kim JJ, Lee HM, Shin DM, Kim W, Yuk JM, Jin HS et al (2012) Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. Cell Host Microbe 11:457–468
Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, Ohsumi Y (2000) The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol 151:263–276
Kirkin V, Lamark T, Sou YS, Bjørkøy G, Nunn JL, Bruun JA, Shvets E et al (2009) A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell 33:505–516
Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G et al (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734
Kuballa P, Huett A, Rioux JD, Daly MJ, Xavier RJ (2008) Impaired autophagy of an intracellular pathogen induced by a Crohn’s disease associated ATG16L1 variant. PLoS One 3(10):e3391. https://doi.org/10.1371/journal.pone.0003391 Epub 2008 Oct 13
Lam KK, Zheng X, Forestieri R, Balgi AD, Nodwell M, Vollett S et al (2012) Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis. PLoS Pathog 8:e1002691. https://doi.org/10.1371/journal.ppat.1002691
Lam GY, Cemma M, Muise AM, Higgins DE, Brumell JH (2013) Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection. Autophagy 9:985–995
Levine B, Packer M, Codogno P (2015) Development of autophagy inducers in clinical medicine. J Clin Invest 125:14–24
Lieberman LA, Higgins DE (2009) A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection. Antimicrob Agents Chemother 53:756–764
Lieberman LA, Higgins DE (2010) Inhibition of Listeria monocytogenes infection by neurological drugs. Int J Antimicrob Agents 35:292–296
Lin L, Baehrecke EH (2015) Autophagy, cell death, and cancer. Mol Cell Oncol 2:e985913. https://doi.org/10.4161/23723556.2014.985913
Lu K, Psakhye I, Jentsch S (2014) A new class of ubiquitin-Atg8 receptors involved in selective autophagy and polyQ protein clearance. Autophagy 10:2381–2382
Mitchell G, Cheng MI, Chen C, Nguyen BN, Whiteley AT, Kianian S, Cox JS et al (2018) Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy. Proc Natl Acad Sci USA 115:E210–E217
Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132
Morenzo-Gonzalo O, Ramirez-Huresca M, Blas-Rus N, Cibrian D, Saiz ML, Jorge I, Camafeita E et al (2017) HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes. PLoS Pathog 13:e1006799. https://doi.org/10.1371/journal.ppat.1006799 eCollection 2017 Dec
Mostowy S, Sancho-Shimizu V, Hamon MA, Simeone R, Brosch R, Johansen T, Cossart P (2011) p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways. J Biol Chem 286:26987–26995
Moy RH, Cherry S (2013) Antimicrobial autophagy: a conserved innate immune response in Drosophila. J Innate Immun 5:444–455
Newman AC, Scholefield CL, Kemp AJ, Newman M, McIver EG, Kamal A, Wilkinson S (2012) TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-κB signaling. PLoS One 7:e50672
Noda T, Fujita N, Yoshimori T (2009) The late stages of autophagy: how does the end begin? Cell Death Differ 16:984–990
Ogawa M, Yoshikawa Y, Mimuro H, Hain T, Chakraborty T, Sasakawa C (2011) Autophagy targeting of Listeria monocytogenes and the bacterial countermeasure. Autophagy 7:310–314
Osawa T, Mizuno Y, Fujita Y, Takatama M, Nakazato Y, Okamoto K (2011) Optineurin in neurodegenerative diseases. Neuropathol Off J Japan Soc Neuropathol 31:569–574
Owen KA, Meyer CB, Bouton AH, Casanova JE (2014) Activation of focal adhesion kinase by Salmonella suppresses autophagy via an Akt/mTOR signaling pathway and promotes bacterial survival in macrophages. PLoS Pathog 10:e1004159. https://doi.org/10.1371/journal.ppat.1004159 eCollection 2014
Parihar SP, Guler R, Lang DM, Harukazu S, David Marais A, Brombacher F, Ratner AJ (2013) Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting listeria-induced Phagosomal escape. PLoS One 8(9):e75490
Parihar SP, Guler R, Khutlang R, Lang DM, Hurdayal R, Mhlanga MM et al (2014) Statin therapy reduces the Mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation. J Infect Dis 209:754–763
Proikas-Cezanne T, Takacs Z, Dönnes P, Kohlbacher O (2015) WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome. J Cell Sci 128:207–217
Puri M, La Pietra L, Mraheil MA, Lucas R, Chakraborty T and Pillich H. 2017. Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes. Toxins (Basel) 9:273. pii: E273. https://doi.org/10.3390/toxins9090273
Py BF, Lipinski MM, Yuan J (2007) Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection. Autophagy 3:117–125
Rhee HW, Zou P, Udeshi ND, Martell JD, Mootha VK, Carr SA et al (2013) Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 339:1328–1331
Rich KA, Burkett C, Webster P (2003) Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol 5:455–468
Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604
Russell RC, Tian Y, Yuan H et al (2013) ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol 15:741–750
Samson E (1981) Xenophagy. Br Dent J 150:136
Sanjurjo L, Amézaga N, Vilaplana C, Cáceres N, Marzo E, Valeri M et al (2013) The scavenger protein apoptosis inhibitor of macrophages (AIM) potentiates the antimicrobial response against Mycobacterium tuberculosis by enhancing autophagy. PLoS One 8:e79670. https://doi.org/10.1371/journal.pone.0079670 eCollection 2013
Sharma G, Dutta RK, Khan MA, Ishaq M, Sharma K, Malhotra H (2014) IL-27 inhibits IFN-γ induced autophagy by concomitant induction of JAK/PI3 K/Akt/mTOR cascade and up-regulation of Mcl-1 in Mycobacterium tuberculosis H37Rv infected macrophages. Int J Biochem Cell Biol 55:335–347. https://doi.org/10.1016/j.biocel.2014.08.022 Epub 2014 Sep 4
Tattoli I, Sorbara MT, Vuckovic D, Ling A, Soares F, Carneiro LA, Yang C, Emili A, Philpott DJ, Girardin SE (2012) Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11:563–575
Tattoli I, Sorbara MT, Yang C, Tooze SA, Philpott DJ, Girardin SE (2013) Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures. EMBO J 32:3066–3078
Thomas M, Mesquita FS, Holden DW (2012) The DUB-ious lack of ALIS in Salmonella infection: a Salmonella deubiquitinase regulates the autophagy of protein aggregates. Autophagy 8:1824–1826
Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F (2009) The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol 10:1215–1221
Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F (2012) Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482:414–418
Tumbarello DA, Manna PT, Allen M, Bycroft M, Arden SD, Kendrick-Jones J, Buss F (2015) The autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of Salmonella typhimurium by autophagy. PLoS Pathog 11:e1005174. https://doi.org/10.1371/journal.ppat.1005174 eCollection 2015
Verlhac P, Viret C, Faure M (2015) Dual function of CALCOCO2/NDP52 during xenophagy. Autophagy 11:965–966. https://doi.org/10.1080/15548627.2015.1046672
Wang J, Yang K, Zhou L, Minhaowu WY, Zhu M et al (2013) MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb. PLoS Pathog 9:e1003697. https://doi.org/10.1371/journal.ppat.1003697 Epub 2013 Oct 10
Watson RO, Manzanillo PS, Cox JS (2012) Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 150:803–815. https://doi.org/10.1016/j.cell.2012.06.040
Watson RO, Bell SL, MacDuff DA, Kimmey JM, Diner EJ, Olivas J (2015) The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy. Cell Host Microbe 17:811–819. https://doi.org/10.1016/j.chom.2015.05.004 Epub 2015 Jun 2
Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B et al (2011) Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333:228–233
Yoshikawa Y, Ogawa M, Hain T, Yoshida M, Fukumatsu M, Kim M, Mimuro H et al (2009) Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat Cell Biol 11:1233–1240
Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J (2007) Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA 104:19023–19028
Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell JH (2009) The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol 183:5909–5916
Acknowledgments
M.P. is thankful to T.C. for guidance, laboratory facilitites and financial assistance. This work was supported by the LISTRESS and PROANTILIS networks of the EU ERANet pathogenomics program to T.C.
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Puri, M., Chakraborty, T., Pillich, H. (2018). Autophagy: A Potential Antibacterial Therapeutic Target. In: Singh, P. (eds) Infectious Diseases and Your Health. Springer, Singapore. https://doi.org/10.1007/978-981-13-1577-0_10
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DOI: https://doi.org/10.1007/978-981-13-1577-0_10
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