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Pathogenesis: New Insights through Advanced Methodologies

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Pamela Schnupf1, Philippe J. Sansonetti2
  • Editors: Pascale Cossart3, Craig R. Roy4, Philippe Sansonetti5
    Affiliations: 1: Institut Imagine, Laboratory of Intestinal Immunity, INSERM UMR1163; Institut Necker Enfants Malades, Laboratory of Host-Microbiota Interaction, INSERM U1151; and Université Paris Descartes-Sorbonne, 75006 Paris, France; 2: Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, and College de France, Paris, France; 3: Institut Pasteur, Paris, France; 4: Yale University School of Medicine, New Haven, Connecticut; 5: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
  • Received 17 January 2019 Accepted 15 February 2019 Published 12 April 2019
  • Pamela Schnupf, [email protected]; Philippe J. Sansonetti, [email protected]
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  • Abstract:

    is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp. have also served as model pathogens in the study of bacterial pathogenesis, and has become one of the best-studied pathogens on a molecular, cellular, and tissue level. In the arms race between and the host immune system, has developed highly sophisticated mechanisms to subvert host cell processes in order to promote infection, escape immune detection, and prevent bacterial clearance. Here, we give an overview of pathogenesis while highlighting innovative techniques and methods whose application has significantly advanced our understanding of pathogenesis in recent years.

  • Citation: Schnupf P, Sansonetti P. 2019. Pathogenesis: New Insights through Advanced Methodologies. Microbiol Spectrum 7(2):BAI-0023-2019. doi:10.1128/microbiolspec.BAI-0023-2019.


1. Trofa AF, Ueno-Olsen H, Oiwa R, Yoshikawa M. 1999. Dr. Kiyoshi Shiga: discoverer of the dysentery bacillus. Clin Infect Dis 29:1303–1306 http://dx.doi.org/10.1086/313437. [PubMed]
2. Anderson M, Sansonetti PJ, Marteyn BS. 2016. Shigella diversity and changing landscape: insights for the twenty-first century. Front Cell Infect Microbiol 6:45 http://dx.doi.org/10.3389/fcimb.2016.00045. [PubMed]
3. Schroeder GN, Hilbi H. 2008. Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion. Clin Microbiol Rev 21:134–156 http://dx.doi.org/10.1128/CMR.00032-07. [PubMed]
4. Muthuirulandi Sethuvel DP, Devanga Ragupathi NK, Anandan S, Veeraraghavan B. 2017. Update on: Shigella new serogroups/serotypes and their antimicrobial resistance. Lett Appl Microbiol 64:8–18 http://dx.doi.org/10.1111/lam.12690. [PubMed]
5. Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi AKM. 2018. Shigellosis. Lancet 391:801–812 http://dx.doi.org/10.1016/S0140-6736(17)33296-8.
6. Hosangadi D, Smith PG, Giersing BK. 2017. Considerations for using ETEC and Shigella disease burden estimates to guide vaccine development strategy. Vaccine S0264-410X(17)31343-9.
7. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acácio S, Biswas K, O’Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209–222 http://dx.doi.org/10.1016/S0140-6736(13)60844-2.
8. Kasper CA, Sorg I, Schmutz C, Tschon T, Wischnewski H, Kim ML, Arrieumerlou C. 2010. Cell-cell propagation of NF-κB transcription factor and MAP kinase activation amplifies innate immunity against bacterial infection. Immunity 33:804–816 http://dx.doi.org/10.1016/j.immuni.2010.10.015. [PubMed]
9. Raqib R, Ekberg C, Sharkar P, Bardhan PK, Zychlinsky A, Sansonetti PJ, Andersson J. 2002. Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2. Infect Immun 70:3199–3207 http://dx.doi.org/10.1128/IAI.70.6.3199-3207.2002. [PubMed]
10. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–1535 http://dx.doi.org/10.1126/science.1092385. [PubMed]
11. Parsot C. 2009. Shigella type III secretion effectors: how, where, when, for what purposes? Curr Opin Microbiol 12:110–116 http://dx.doi.org/10.1016/j.mib.2008.12.002.
12. Mattock E, Blocker AJ. 2017. How do the virulence factors of Shigella work together to cause disease? Front Cell Infect Microbiol 7:64 http://dx.doi.org/10.3389/fcimb.2017.00064. [PubMed]
13. Demers J-P, Habenstein B, Loquet A, Kumar Vasa S, Giller K, Becker S, Baker D, Lange A, Sgourakis NG. 2014. High-resolution structure of the Shigella type-III secretion needle by solid-state NMR and cryo-electron microscopy. Nat Commun 5:4976 http://dx.doi.org/10.1038/ncomms5976. [PubMed]
14. Dohlich K, Zumsteg AB, Goosmann C, Kolbe M. 2014. A substrate-fusion protein is trapped inside the type III secretion system channel in Shigella flexneri. PLoS Pathog 10:e1003881 http://dx.doi.org/10.1371/journal.ppat.1003881. [PubMed]
15. Epler CR, Dickenson NE, Bullitt E, Picking WL. 2012. Ultrastructural analysis of IpaD at the tip of the nascent MxiH type III secretion apparatus of Shigella flexneri. J Mol Biol 420:29–39 http://dx.doi.org/10.1016/j.jmb.2012.03.025. [PubMed]
16. Barta ML, Guragain M, Adam P, Dickenson NE, Patil M, Geisbrecht BV, Picking WL, Picking WD. 2012. Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure. Proteins 80:935–945 http://dx.doi.org/10.1002/prot.23251. [PubMed]
17. van der Goot FG, Tran Van Nhieu G, Allaoui A, Sansonetti P, Lafont F. 2004. Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism. J Biol Chem 279:47792–47798 http://dx.doi.org/10.1074/jbc.M406824200. [PubMed]
18. Hayward RD, Cain RJ, McGhie EJ, Phillips N, Garner MJ, Koronakis V. 2005. Cholesterol binding by the bacterial type III translocon is essential for virulence effector delivery into mammalian cells. Mol Microbiol 56:590–603 http://dx.doi.org/10.1111/j.1365-2958.2005.04568.x. [PubMed]
19. Roehrich AD, Bordignon E, Mode S, Shen D-K, Liu X, Pain M, Murillo I, Martinez-Argudo I, Sessions RB, Blocker AJ. 2017. Steps for Shigella gatekeeper protein MxiC function in hierarchical type III secretion regulation. J Biol Chem 292:1705–1723 http://dx.doi.org/10.1074/jbc.M116.746826. [PubMed]
20. Parsot C, Ageron E, Penno C, Mavris M, Jamoussi K, d’Hauteville H, Sansonetti P, Demers B. 2005. A secreted anti-activator, OspD1, and its chaperone, Spa15, are involved in the control of transcription by the type III secretion apparatus activity in Shigella flexneri. Mol Microbiol 56:1627–1635 http://dx.doi.org/10.1111/j.1365-2958.2005.04645.x. [PubMed]
21. Campbell-Valois F-X, Schnupf P, Nigro G, Sachse M, Sansonetti PJ, Parsot C. 2014. A fluorescent reporter reveals on/off regulation of the Shigella type III secretion apparatus during entry and cell-to-cell spread. Cell Host Microbe 15:177–189 http://dx.doi.org/10.1016/j.chom.2014.01.005. [PubMed]
22. Mou X, Souter S, Du J, Reeves AZ, Lesser CF. 2018. Synthetic bottom-up approach reveals the complex interplay of Shigella effectors in regulation of epithelial cell death. Proc Natl Acad Sci USA 115:6452–6457 http://dx.doi.org/10.1073/pnas.1801310115. [PubMed]
23. Bergounioux J, Elisee R, Prunier A-L, Donnadieu F, Sperandio B, Sansonetti P, Arbibe L. 2012. Calpain activation by the Shigella flexneri effector VirA regulates key steps in the formation and life of the bacterium’s epithelial niche. Cell Host Microbe 11:240–252 http://dx.doi.org/10.1016/j.chom.2012.01.013. [PubMed]
24. Ashida H, Sasakawa C. 2016. Shigella IpaH family effectors as a versatile model for studying pathogenic bacteria. Front Cell Infect Microbiol 5:100 http://dx.doi.org/10.3389/fcimb.2015.00100. [PubMed]
25. Rohde JR, Breitkreutz A, Chenal A, Sansonetti PJ, Parsot C. 2007. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe 1:77–83 http://dx.doi.org/10.1016/j.chom.2007.02.002. [PubMed]
26. Ashida H, Sasakawa C. 2017. Bacterial E3 ligase effectors exploit host ubiquitin systems. Curr Opin Microbiol 35:16–22 http://dx.doi.org/10.1016/j.mib.2016.11.001. [PubMed]
27. Martino MC, Rossi G, Martini I, Tattoli I, Chiavolini D, Phalipon A, Sansonetti PJ, Bernardini ML. 2005. Mucosal lymphoid infiltrate dominates colonic pathological changes in murine experimental shigellosis. J Infect Dis 192:136–148 http://dx.doi.org/10.1086/430740. [PubMed]
28. Anderson MC, Vonaesch P, Saffarian A, Marteyn BS, Sansonetti PJ. 2017. Shigella sonnei encodes a functional T6SS used for interbacterial competition and niche occupancy. Cell Host Microbe 21:769–776.e3 http://dx.doi.org/10.1016/j.chom.2017.05.004. [PubMed]
29. Yang G, Wang L, Wang Y, Li P, Zhu J, Qiu S, Hao R, Wu Z, Li W, Song H. 2015. hfq regulates acid tolerance and virulence by responding to acid stress in Shigella flexneri. Res Microbiol 166:476–485 http://dx.doi.org/10.1016/j.resmic.2015.06.007. [PubMed]
30. Brotcke Zumsteg A, Goosmann C, Brinkmann V, Morona R, Zychlinsky A. 2014. IcsA is a Shigella flexneri adhesin regulated by the type III secretion system and required for pathogenesis. Cell Host Microbe 15:435–445 http://dx.doi.org/10.1016/j.chom.2014.03.001. [PubMed]
31. Faherty CS, Redman JC, Rasko DA, Barry EM, Nataro JP. 2012. Shigella flexneri effectors OspE1 and OspE2 mediate induced adherence to the colonic epithelium following bile salts exposure. Mol Microbiol 85:107–121 http://dx.doi.org/10.1111/j.1365-2958.2012.08092.x. [PubMed]
32. Vergara-Irigaray M, Fookes MC, Thomson NR, Tang CM. 2014. RNA-seq analysis of the influence of anaerobiosis and FNR on Shigella flexneri. BMC Genomics 15:438 http://dx.doi.org/10.1186/1471-2164-15-438. [PubMed]
33. Marteyn B, West NP, Browning DF, Cole JA, Shaw JG, Palm F, Mounier J, Prévost M-C, Sansonetti P, Tang CM. 2010. Modulation of Shigella virulence in response to available oxygen in vivo. Nature 465:355–358 http://dx.doi.org/10.1038/nature08970. [PubMed]
34. Sansonetti PJ, Arondel J, Fontaine A, d’Hauteville H, Bernardini ML. 1991. OmpB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. Vaccine 9:416–422 http://dx.doi.org/10.1016/0264-410X(91)90128-S.
35. Mathan MM, Mathan VI. 1991. Morphology of rectal mucosa of patients with shigellosis. Rev Infect Dis 13(Suppl 4) :S314–S318 http://dx.doi.org/10.1093/clinids/13.Supplement_4.S314. [PubMed]
36. Sansonetti PJ, Arondel J, Cantey JR, Prévost MC, Huerre M. 1996. Infection of rabbit Peyer’s patches by Shigella flexneri: effect of adhesive or invasive bacterial phenotypes on follicle-associated epithelium. Infect Immun 64:2752–2764. [PubMed]
37. Wassef JS, Keren DF, Mailloux JL. 1989. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect Immun 57:858–863. [PubMed]
38. Perdomo OJ, Cavaillon JM, Huerre M, Ohayon H, Gounon P, Sansonetti PJ. 1994. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J Exp Med 180:1307–1319 http://dx.doi.org/10.1084/jem.180.4.1307. [PubMed]
39. Shim D-H, Suzuki T, Chang S-Y, Park S-M, Sansonetti PJ, Sasakawa C, Kweon M-N. 2007. New animal model of shigellosis in the guinea pig: its usefulness for protective efficacy studies. J Immunol 178:2476–2482 http://dx.doi.org/10.4049/jimmunol.178.4.2476. [PubMed]
40. Romero S, Grompone G, Carayol N, Mounier J, Guadagnini S, Prevost M-C, Sansonetti PJ, Tran Van Nhieu GT. 2011. ATP-mediated Erk1/2 activation stimulates bacterial capture by filopodia, which precedes Shigella invasion of epithelial cells. Cell Host Microbe 9:508–519 http://dx.doi.org/10.1016/j.chom.2011.05.005. [PubMed]
41. Romero S, Quatela A, Bornschlögl T, Guadagnini S, Bassereau P, Tran Van Nhieu G. 2012. Filopodium retraction is controlled by adhesion to its tip. J Cell Sci 125:4999–5004. ERRATUM J Cell Sci 125:5587 http://dx.doi.org/10.1242/jcs.104778. [PubMed]
42. Xu D, Liao C, Zhang B, Tolbert WD, He W, Dai Z, Zhang W, Yuan W, Pazgier M, Liu J, Yu J, Sansonetti PJ, Bevins CL, Shao Y, Lu W. 2018. Human enteric α-defensin 5 promotes Shigella infection by enhancing bacterial adhesion and invasion. Immunity 48:1233–1244.e6 http://dx.doi.org/10.1016/j.immuni.2018.04.014. [PubMed]
43. Arena ET, Campbell-Valois F-X, Tinevez J-Y, Nigro G, Sachse M, Moya-Nilges M, Nothelfer K, Marteyn B, Shorte SL, Sansonetti PJ. 2015. Bioimage analysis of Shigella infection reveals targeting of colonic crypts. Proc Natl Acad Sci USA 112:E3282–E3290 http://dx.doi.org/10.1073/pnas.1509091112. [PubMed]
44. Nothelfer K, Arena ET, Pinaud L, Neunlist M, Mozeleski B, Belotserkovsky I, Parsot C, Dinadayala P, Burger-Kentischer A, Raqib R, Sansonetti PJ, Phalipon A. 2014. B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection. J Exp Med 211:1215–1229 http://dx.doi.org/10.1084/jem.20130914. [PubMed]
45. Miller H, Zhang J, Kuolee R, Patel GB, Chen W. 2007. Intestinal M cells: the fallible sentinels? World J Gastroenterol 13:1477–1486 http://dx.doi.org/10.3748/wjg.v13.i10.1477. [PubMed]
46. Jensen VB, Harty JT, Jones BD. 1998. Interactions of the invasive pathogens Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells and murine Peyer’s patches. Infect Immun 66:3758–3766. [PubMed]
47. Ashida H, Kim M, Sasakawa C. 2014. Manipulation of the host cell death pathway by Shigella. Cell Microbiol 16:1757–1766 http://dx.doi.org/10.1111/cmi.12367. [PubMed]
48. Jorgensen I, Miao EA. 2015. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265:130–142 http://dx.doi.org/10.1111/imr.12287. [PubMed]
49. Shi J, Gao W, Shao F. 2017. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 42:245–254 http://dx.doi.org/10.1016/j.tibs.2016.10.004. [PubMed]
50. Storek KM, Monack DM. 2015. Bacterial recognition pathways that lead to inflammasome activation. Immunol Rev 265:112–129 http://dx.doi.org/10.1111/imr.12289. [PubMed]
51. Hermansson A-K, Paciello I, Bernardini ML. 2016. The orchestra and its maestro: Shigella’s fine-tuning of the inflammasome platforms. Curr Top Microbiol Immunol 397:91–115 http://dx.doi.org/10.1007/978-3-319-41171-2_5.
52. Suzuki S, Franchi L, He Y, Muñoz-Planillo R, Mimuro H, Suzuki T, Sasakawa C, Núñez G. 2014. Shigella type III secretion protein MxiI is recognized by Naip2 to induce Nlrc4 inflammasome activation independently of Pkcδ. PLoS Pathog 10:e1003926 http://dx.doi.org/10.1371/journal.ppat.1003926.
53. Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, Leaf IA, Aderem A. 2010. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci USA 107:3076–3080 http://dx.doi.org/10.1073/pnas.0913087107.
54. Yang J, Zhao Y, Shi J, Shao F. 2013. Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation. Proc Natl Acad Sci USA 110:14408–14413 http://dx.doi.org/10.1073/pnas.1306376110.
55. Rayamajhi M, Zak DE, Chavarria-Smith J, Vance RE, Miao EA. 2013. Cutting edge: mouse NAIP1 detects the type III secretion system needle protein. J Immunol 191:3986–3989 http://dx.doi.org/10.4049/jimmunol.1301549.
56. Watarai M, Funato S, Sasakawa C. 1996. Interaction of Ipa proteins of Shigella flexneri with α5β1 integrin promotes entry of the bacteria into mammalian cells. J Exp Med 183:991–999 http://dx.doi.org/10.1084/jem.183.3.991.
57. Skoudy A, Mounier J, Aruffo A, Ohayon H, Gounon P, Sansonetti P, Tran Van Nhieu G. 2000. CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells. Cell Microbiol 2:19–33 http://dx.doi.org/10.1046/j.1462-5822.2000.00028.x.
58. Russo BC, Stamm LM, Raaben M, Kim CM, Kahoud E, Robinson LR, Bose S, Queiroz AL, Herrera BB, Baxt LA, Mor-Vaknin N, Fu Y, Molina G, Markovitz DM, Whelan SP, Goldberg MB. 2016. Intermediate filaments enable pathogen docking to trigger type 3 effector translocation. Nat Microbiol 1:16025 http://dx.doi.org/10.1038/nmicrobiol.2016.25.
59. Tran Van Nhieu G, Caron E, Hall A, Sansonetti PJ. 1999. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J 18:3249–3262 http://dx.doi.org/10.1093/emboj/18.12.3249.
60. Tran Van Nhieu G, Ben-Ze’ev A, Sansonetti PJ. 1997. Modulation of bacterial entry into epithelial cells by association between vinculin and the Shigella IpaA invasin. EMBO J 16:2717–2729 http://dx.doi.org/10.1093/emboj/16.10.2717.
61. Izard T, Tran Van Nhieu G, Bois PRJ. 2006. Shigella applies molecular mimicry to subvert vinculin and invade host cells. J Cell Biol 175:465–475 http://dx.doi.org/10.1083/jcb.200605091.
62. Yoshida S, Handa Y, Suzuki T, Ogawa M, Suzuki M, Tamai A, Abe A, Katayama E, Sasakawa C. 2006. Microtubule-severing activity of Shigella is pivotal for intercellular spreading. Science 314:985–989 http://dx.doi.org/10.1126/science.1133174.
63. Germane KL, Ohi R, Goldberg MB, Spiller BW. 2008. Structural and functional studies indicate that Shigella VirA is not a protease and does not directly destabilize microtubules. Biochemistry 47:10241–10243 http://dx.doi.org/10.1021/bi801533k.
64. Niebuhr K, Giuriato S, Pedron T, Philpott DJ, Gaits F, Sable J, Sheetz MP, Parsot C, Sansonetti PJ, Payrastre B. 2002. Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology. EMBO J 21:5069–5078 http://dx.doi.org/10.1093/emboj/cdf522.
65. Bonnet M, Tran Van Nhieu G. 2016. How Shigella utilizes Ca(2+) jagged edge signals during invasion of epithelial cells. Front Cell Infect Microbiol 6:16 http://dx.doi.org/10.3389/fcimb.2016.00016.
66. Tran Van Nhieu G, Kai Liu B, Zhang J, Pierre F, Prigent S, Sansonetti P, Erneux C, Kuk Kim J, Suh P-G, Dupont G, Combettes L. 2013. Actin-based confinement of calcium responses during Shigella invasion. Nat Commun 4:1567 http://dx.doi.org/10.1038/ncomms2561.
67. Sun CH, Wacquier B, Aguilar DI, Carayol N, Denis K, Boucherie S, Valencia-Gallardo C, Simsek C, Erneux C, Lehman A, Enninga J, Arbibe L, Sansonetti P, Dupont G, Combettes L, Tran Van Nhieu G. 2017. The Shigella type III effector IpgD recodes Ca 2+ signals during invasion of epithelial cells. EMBO J 36:2567–2580 http://dx.doi.org/10.15252/embj.201696272.
68. Weiner A, Mellouk N, Lopez-Montero N, Chang Y-Y, Souque C, Schmitt C, Enninga J. 2016. Macropinosomes are key players in early Shigella invasion and vacuolar escape in epithelial cells. PLoS Pathog 12:e1005602 http://dx.doi.org/10.1371/journal.ppat.1005602.
69. High N, Mounier J, Prévost MC, Sansonetti PJ. 1992. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J 11:1991–1999 http://dx.doi.org/10.1002/j.1460-2075.1992.tb05253.x.
70. Mellouk N, Weiner A, Aulner N, Schmitt C, Elbaum M, Shorte SL, Danckaert A, Enninga J. 2014. Shigella subverts the host recycling compartment to rupture its vacuole. Cell Host Microbe 16:517–530 http://dx.doi.org/10.1016/j.chom.2014.09.005.
71. Krokowski S, Mostowy S. 2016. Interactions between Shigella flexneri and the autophagy machinery. Front Cell Infect Microbiol 6:17 http://dx.doi.org/10.3389/fcimb.2016.00017.
72. Travassos LH, Carneiro LAM, Ramjeet M, Hussey S, Kim Y-G, Magalhães JG, Yuan L, Soares F, Chea E, Le Bourhis L, Boneca IG, Allaoui A, Jones NL, Nuñez G, Girardin SE, Philpott DJ. 2010. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 11:55–62 http://dx.doi.org/10.1038/ni.1823.
73. Tattoli I, Sorbara MT, Vuckovic D, Ling A, Soares F, Carneiro LAM, 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 http://dx.doi.org/10.1016/j.chom.2012.04.012.
74. Sorbara MT, Foerster EG, Tsalikis J, Abdel-Nour M, Mangiapane J, Sirluck-Schroeder I, Tattoli I, van Dalen R, Isenman DE, Rohde JR, Girardin SE, Philpott DJ. 2018. Complement C3 drives autophagy-dependent restriction of cyto-invasive bacteria. Cell Host Microbe 23:644–652.e5 http://dx.doi.org/10.1016/j.chom.2018.04.008.
75. Baxt LA, Goldberg MB. 2014. Host and bacterial proteins that repress recruitment of LC3 to Shigella early during infection. PLoS One 9:e94653 http://dx.doi.org/10.1371/journal.pone.0094653.
76. Liu W, Zhou Y, Peng T, Zhou P, Ding X, Li Z, Zhong H, Xu Y, Chen S, Hang HC, Shao F. 2018. N ε-fatty acylation of multiple membrane-associated proteins by Shigella IcsB effector to modulate host function. Nat Microbiol 3:996–1009 http://dx.doi.org/10.1038/s41564-018-0215-6.
77. Agaisse H. 2016. Molecular and cellular mechanisms of Shigella flexneri dissemination. Front Cell Infect Microbiol 6:29 http://dx.doi.org/10.3389/fcimb.2016.00029.
78. Monack DM, Theriot JA. 2001. Actin-based motility is sufficient for bacterial membrane protrusion formation and host cell uptake. Cell Microbiol 3:633–647 http://dx.doi.org/10.1046/j.1462-5822.2001.00143.x.
79. Fukumatsu M, Ogawa M, Arakawa S, Suzuki M, Nakayama K, Shimizu S, Kim M, Mimuro H, Sasakawa C. 2012. Shigella targets epithelial tricellular junctions and uses a noncanonical clathrin-dependent endocytic pathway to spread between cells. Cell Host Microbe 11:325–336 http://dx.doi.org/10.1016/j.chom.2012.03.001.
80. Torraca V, Mostowy S. 2016. Septins and bacterial infection. Front Cell Dev Biol 4:127 http://dx.doi.org/10.3389/fcell.2016.00127.
81. 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 http://dx.doi.org/10.1074/jbc.M111.223610.
82. Sirianni A, Krokowski S, Lobato-Márquez D, Buranyi S, Pfanzelter J, Galea D, Willis A, Culley S, Henriques R, Larrouy-Maumus G, Hollinshead M, Sancho-Shimizu V, Way M, Mostowy S. 2016. Mitochondria mediate septin cage assembly to promote autophagy of Shigella. EMBO Rep 17:1029–1043 http://dx.doi.org/10.15252/embr.201541832.
83. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. 2005. Escape of intracellular Shigella from autophagy. Science 307:727–731 http://dx.doi.org/10.1126/science.1106036.
84. Mostowy S, Boucontet L, Mazon Moya MJ, Sirianni A, Boudinot P, Hollinshead M, Cossart P, Herbomel P, Levraud J-P, Colucci-Guyon E. 2013. The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy. PLoS Pathog 9:e1003588 http://dx.doi.org/10.1371/journal.ppat.1003588.
85. Uchiya K, Tobe T, Komatsu K, Suzuki T, Watarai M, Fukuda I, Yoshikawa M, Sasakawa C. 1995. Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading. Mol Microbiol 17:241–250 http://dx.doi.org/10.1111/j.1365-2958.1995.mmi_17020241.x.
86. Huang J, Brumell JH. 2014. Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol 12:101–114 http://dx.doi.org/10.1038/nrmicro3160.
87. Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F. 2012. Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 inactivation to counteract host defenses. Cell 150:1029–1041 http://dx.doi.org/10.1016/j.cell.2012.06.050.
88. Campbell-Valois F-X, Sachse M, Sansonetti PJ, Parsot C. 2015. Escape of actively secreting Shigella flexneri from ATG8/LC3-positive vacuoles formed during cell-to-cell spread is facilitated by IcsB and VirA. mBio 6:e02567-14 http://dx.doi.org/10.1128/mBio.02567-14. [PubMed]
89. Li P, Jiang W, Yu Q, Liu W, Zhou P, Li J, Xu J, Xu B, Wang F, Shao F. 2017. Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence. Nature 551:378–383. [PubMed]
90. Piro AS, Hernandez D, Luoma S, Feeley EM, Finethy R, Yirga A, Frickel EM, Lesser CF, Coers J. 2017. Detection of cytosolic Shigella flexneri via a C-terminal triple-arginine motif of GBP1 inhibits actin-based motility. mBio 8:e01979-17 http://dx.doi.org/10.1128/mBio.01979-17. [PubMed]
91. Paciello I, Silipo A, Lembo-Fazio L, Curcurù L, Zumsteg A, Noël G, Ciancarella V, Sturiale L, Molinaro A, Bernardini ML. 2013. Intracellular Shigella remodels its LPS to dampen the innate immune recognition and evade inflammasome activation. Proc Natl Acad Sci USA 110:E4345–E4354. CORRECTION Proc Natl Acad Sci USA 110:20843 http://dx.doi.org/10.1073/pnas.1303641110.
92. Kobayashi T, Ogawa M, Sanada T, Mimuro H, Kim M, Ashida H, Akakura R, Yoshida M, Kawalec M, Reichhart J-M, Mizushima T, Sasakawa C. 2013. The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection. Cell Host Microbe 13:570–583 http://dx.doi.org/10.1016/j.chom.2013.04.012. [PubMed]
93. Mayo LD, Donner DB. 2001. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA 98:11598–11603 http://dx.doi.org/10.1073/pnas.181181198. [PubMed]
94. Ramel D, Lagarrigue F, Pons V, Mounier J, Dupuis-Coronas S, Chicanne G, Sansonetti PJ, Gaits-Iacovoni F, Tronchère H, Payrastre B. 2011. Shigella flexneri infection generates the lipid PI5P to alter endocytosis and prevent termination of EGFR signaling. Sci Signal 4:ra61 http://dx.doi.org/10.1126/scisignal.2001619. [PubMed]
95. Bhola PD, Letai A. 2016. Mitochondria—judges and executioners of cell death sentences. Mol Cell 61:695–704 http://dx.doi.org/10.1016/j.molcel.2016.02.019. [PubMed]
96. Sukumaran SK, Fu NY, Tin CB, Wan KF, Lee SS, Yu VC. 2010. A soluble form of the pilus protein FimA targets the VDAC-hexokinase complex at mitochondria to suppress host cell apoptosis. Mol Cell 37:768–783 http://dx.doi.org/10.1016/j.molcel.2010.02.015. [PubMed]
97. Bravo V, Puhar A, Sansonetti P, Parsot C, Toro CS. 2015. Distinct mutations led to inactivation of type 1 fimbriae expression in Shigella spp. PLoS One 10:e0121785 http://dx.doi.org/10.1371/journal.pone.0121785. [PubMed]
98. Faherty CS, Maurelli AT. 2009. Spa15 of Shigella flexneri is secreted through the type III secretion system and prevents staurosporine-induced apoptosis. Infect Immun 77:5281–5290 http://dx.doi.org/10.1128/IAI.00800-09. [PubMed]
99. Pendaries C, Tronchère H, Arbibe L, Mounier J, Gozani O, Cantley L, Fry MJ, Gaits-Iacovoni F, Sansonetti PJ, Payrastre B. 2006. PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. EMBO J 25:1024–1034 http://dx.doi.org/10.1038/sj.emboj.7601001. [PubMed]
100. Carneiro LAM, Travassos LH, Soares F, Tattoli I, Magalhaes JG, Bozza MT, Plotkowski MC, Sansonetti PJ, Molkentin JD, Philpott DJ, Girardin SE. 2009. Shigella induces mitochondrial dysfunction and cell death in nonmyleoid cells. Cell Host Microbe 5:123–136 http://dx.doi.org/10.1016/j.chom.2008.12.011. [PubMed]
101. Kim M, Ogawa M, Fujita Y, Yoshikawa Y, Nagai T, Koyama T, Nagai S, Lange A, Fässler R, Sasakawa C. 2009. Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment. Nature 459:578–582 http://dx.doi.org/10.1038/nature07952. [PubMed]
102. Miura M, Terajima J, Izumiya H, Mitobe J, Komano T, Watanabe H. 2006. OspE2 of Shigella sonnei is required for the maintenance of cell architecture of bacterium-infected cells. Infect Immun 74:2587–2595 http://dx.doi.org/10.1128/IAI.74.5.2587-2595.2006. [PubMed]
103. Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M, Fujita Y, Muller D, Kirikae T, Jackson PK, Kotani S, Sasakawa C. 2007. A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. Cell 130:611–623 http://dx.doi.org/10.1016/j.cell.2007.06.043. [PubMed]
104. Boal F, Puhar A, Xuereb J-M, Kunduzova O, Sansonetti PJ, Payrastre B, Tronchère H. 2016. PI5P triggers ICAM-1 degradation in Shigella-infected cells, thus dampening immune cell recruitment. Cell Reports 14:750–759 http://dx.doi.org/10.1016/j.celrep.2015.12.079. [PubMed]
105. Pieper R, Fisher CR, Suh M-J, Huang S-T, Parmar P, Payne SM. 2013. Analysis of the proteome of intracellular Shigella flexneri reveals pathways important for intracellular growth. Infect Immun 81:4635–4648 http://dx.doi.org/10.1128/IAI.00975-13. [PubMed]
106. Payne SM, Wyckoff EE, Murphy ER, Oglesby AG, Boulette ML, Davies NML. 2006. Iron and pathogenesis of Shigella: iron acquisition in the intracellular environment. Biometals 19:173–180 http://dx.doi.org/10.1007/s10534-005-4577-x. [PubMed]
107. Kentner D, Martano G, Callon M, Chiquet P, Brodmann M, Burton O, Wahlander A, Nanni P, Delmotte N, Grossmann J, Limenitakis J, Schlapbach R, Kiefer P, Vorholt JA, Hiller S, Bumann D. 2014. Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth. Proc Natl Acad Sci USA 111:9929–9934 http://dx.doi.org/10.1073/pnas.1406694111. [PubMed]
108. Vonaesch P, Campbell-Valois F-X, Dufour A, Sansonetti PJ, Schnupf P. 2016. Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation. Cell Microbiol 18:982–997 http://dx.doi.org/10.1111/cmi.12561. [PubMed]
109. Lu R, Herrera BB, Eshleman HD, Fu Y, Bloom A, Li Z, Sacks DB, Goldberg MB. 2015. Shigella effector OspB activates mTORC1 in a manner that depends on IQGAP1 and promotes cell proliferation. PLoS Pathog 11:e1005200 http://dx.doi.org/10.1371/journal.ppat.1005200. [PubMed]
110. Yu S, Gao N. 2015. Compartmentalizing intestinal epithelial cell toll-like receptors for immune surveillance. Cell Mol Life Sci 72:3343–3353 http://dx.doi.org/10.1007/s00018-015-1931-1. [PubMed]
111. Lee J, Mo J-H, Katakura K, Alkalay I, Rucker AN, Liu Y-T, Lee H-K, Shen C, Cojocaru G, Shenouda S, Kagnoff M, Eckmann L, Ben-Neriah Y, Raz E. 2006. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 8:1327–1336 http://dx.doi.org/10.1038/ncb1500. [PubMed]
112. He Y, Hara H, Núñez G. 2016. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41:1012–1021 http://dx.doi.org/10.1016/j.tibs.2016.09.002. [PubMed]
113. Girardin SE, Tournebize R, Mavris M, Page AL, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ, Philpott DJ. 2001. CARD4/Nod1 mediates NF-κB and JNK activation by invasive Shigella flexneri. EMBO Rep 2:736–742 http://dx.doi.org/10.1093/embo-reports/kve155. [PubMed]
114. Killackey SA, Sorbara MT, Girardin SE. 2016. Cellular aspects of Shigella pathogenesis: focus on the manipulation of host cell processes. Front Cell Infect Microbiol 6:38 http://dx.doi.org/10.3389/fcimb.2016.00038. [PubMed]
115. Gaudet RG, Guo CX, Molinaro R, Kottwitz H, Rohde JR, Dangeard A-S, Arrieumerlou C, Girardin SE, Gray-Owen SD. 2017. Innate recognition of intracellular bacterial growth is driven by the TIFA-dependent cytosolic surveillance pathway. Cell Reports 19:1418–1430 http://dx.doi.org/10.1016/j.celrep.2017.04.063. [PubMed]
116. Sanada T, Kim M, Mimuro H, Suzuki M, Ogawa M, Oyama A, Ashida H, Kobayashi T, Koyama T, Nagai S, Shibata Y, Gohda J, Inoue J, Mizushima T, Sasakawa C. 2012. The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature 483:623–626 http://dx.doi.org/10.1038/nature10894. [PubMed]
117. Nishide A, Kim M, Takagi K, Himeno A, Sanada T, Sasakawa C, Mizushima T. 2013. Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI. J Mol Biol 425:2623–2631 http://dx.doi.org/10.1016/j.jmb.2013.02.037. [PubMed]
118. Ashida H, Nakano H, Sasakawa C. 2013. Shigella IpaH0722 E3 ubiquitin ligase effector targets TRAF2 to inhibit PKC-NF-κB activity in invaded epithelial cells. PLoS Pathog 9:e1003409 http://dx.doi.org/10.1371/journal.ppat.1003409. [PubMed]
119. de Jong MF, Liu Z, Chen D, Alto NM. 2016. Shigella flexneri suppresses NF-κB activation by inhibiting linear ubiquitin chain ligation. Nat Microbiol 1:16084 http://dx.doi.org/10.1038/nmicrobiol.2016.84. [PubMed]
120. Zhang Y, Mühlen S, Oates CV, Pearson JS, Hartland EL. 2016. Identification of a distinct substrate-binding domain in the bacterial cysteine methyltransferase effectors NleE and OspZ. J Biol Chem 291:20149–20162 http://dx.doi.org/10.1074/jbc.M116.734079. [PubMed]
121. Newton HJ, Pearson JS, Badea L, Kelly M, Lucas M, Holloway G, Wagstaff KM, Dunstone MA, Sloan J, Whisstock JC, Kaper JB, Robins-Browne RM, Jans DA, Frankel G, Phillips AD, Coulson BS, Hartland EL. 2010. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathog 6:e1000898 http://dx.doi.org/10.1371/journal.ppat.1000898. [PubMed]
122. Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C. 2010. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKγ to dampen the host NF-κB-mediated inflammatory response. Nat Cell Biol 12 :66–73. [PubMed]
123. Kim DW, Lenzen G, Page A-L, Legrain P, Sansonetti PJ, Parsot C. 2005. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc Natl Acad Sci USA 102:14046–14051 http://dx.doi.org/10.1073/pnas.0504466102. [PubMed]
124. Wang F, Jiang Z, Li Y, He X, Zhao J, Yang X, Zhu L, Yin Z, Li X, Wang X, Liu W, Shang W, Yang Z, Wang S, Zhen Q, Zhang Z, Yu Y, Zhong H, Ye Q, Huang L, Yuan J. 2013. Shigella flexneri T3SS effector IpaH4.5 modulates the host inflammatory response via interaction with NF-κB p65 protein. Cell Microbiol 15:474–485 http://dx.doi.org/10.1111/cmi.12052. [PubMed]
125. Li H, Xu H, Zhou Y, Zhang J, Long C, Li S, Chen S, Zhou J-M, Shao F. 2007. The phosphothreonine lyase activity of a bacterial type III effector family. Science 315:1000–1003 http://dx.doi.org/10.1126/science.1138960. [PubMed]
126. Arbibe L, Kim DW, Batsche E, Pedron T, Mateescu B, Muchardt C, Parsot C, Sansonetti PJ. 2007. An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses. Nat Immunol 8:47–56 http://dx.doi.org/10.1038/ni1423. [PubMed]
127. Harouz H, Rachez C, Meijer BM, Marteyn B, Donnadieu F, Cammas F, Muchardt C, Sansonetti P, Arbibe L. 2014. Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF. EMBO J 33:2606–2622 http://dx.doi.org/10.15252/embj.201489244. [PubMed]
128. Schmutz C, Ahrné E, Kasper CA, Tschon T, Sorg I, Dreier RF, Schmidt A, Arrieumerlou C. 2013. Systems-level overview of host protein phosphorylation during Shigella flexneri infection revealed by phosphoproteomics. Mol Cell Proteomics 12:2952–2968 http://dx.doi.org/10.1074/mcp.M113.029918. [PubMed]
129. Okuda J, Toyotome T, Kataoka N, Ohno M, Abe H, Shimura Y, Seyedarabi A, Pickersgill R, Sasakawa C. 2005. Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses. Biochem Biophys Res Commun 333:531–539 http://dx.doi.org/10.1016/j.bbrc.2005.05.145. [PubMed]
130. Burnaevskiy N, Fox TG, Plymire DA, Ertelt JM, Weigele BA, Selyunin AS, Way SS, Patrie SM, Alto NM. 2013. Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ. Nature 496:106–109 http://dx.doi.org/10.1038/nature12004. [PubMed]
131. Dobbs N, Burnaevskiy N, Chen D, Gonugunta VK, Alto NM, Yan N. 2015. STING activation by translocation from the ER is associated with infection and autoinflammatory disease. Cell Host Microbe 18:157–168 http://dx.doi.org/10.1016/j.chom.2015.07.001. [PubMed]
132. Mounier J, Boncompain G, Senerovic L, Lagache T, Chrétien F, Perez F, Kolbe M, Olivo-Marin J-C, Sansonetti PJ, Sauvonnet N. 2012. Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex and recycling network to inhibit host cell secretion. Cell Host Microbe 12:381–389 http://dx.doi.org/10.1016/j.chom.2012.07.010. [PubMed]
133. Zheng Z, Wei C, Guan K, Yuan Y, Zhang Y, Ma S, Cao Y, Wang F, Zhong H, He X. 2016. Bacterial E3 ubiquitin ligase IpaH4.5 of Shigella flexneri targets TBK1 to dampen the host antibacterial response. J Immunol 196:1199–1208 http://dx.doi.org/10.4049/jimmunol.1501045. [PubMed]
134. Puhar A, Tronchère H, Payrastre B, Tran Van Nhieu GTV, Sansonetti PJ. 2013. A Shigella effector dampens inflammation by regulating epithelial release of danger signal ATP through production of the lipid mediator PtdIns5P. Immunity 39:1121–1131 http://dx.doi.org/10.1016/j.immuni.2013.11.013. [PubMed]
135. Konradt C, Frigimelica E, Nothelfer K, Puhar A, Salgado-Pabón W, di Bartolo V, Scott-Algara D, Rodrigues CD, Sansonetti PJ, Phalipon A. 2011. The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism. Cell Host Microbe 9:263–272 http://dx.doi.org/10.1016/j.chom.2011.03.010. [PubMed]
136. Salgado-Pabón W, Celli S, Arena ET, Nothelfer K, Roux P, Sellge G, Frigimelica E, Bousso P, Sansonetti PJ, Phalipon A. 2013. Shigella impairs T lymphocyte dynamics in vivo. Proc Natl Acad Sci USA 110:4458–4463 http://dx.doi.org/10.1073/pnas.1300981110. [PubMed]
137. Pinaud L, Samassa F, Porat Z, Ferrari ML, Belotserkovsky I, Parsot C, Sansonetti PJ, Campbell-Valois F-X, Phalipon A. 2017. Injection of T3SS effectors not resulting in invasion is the main targeting mechanism of Shigella toward human lymphocytes. Proc Natl Acad Sci USA 114:9954–9959 http://dx.doi.org/10.1073/pnas.1707098114. [PubMed]

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is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp. have also served as model pathogens in the study of bacterial pathogenesis, and has become one of the best-studied pathogens on a molecular, cellular, and tissue level. In the arms race between and the host immune system, has developed highly sophisticated mechanisms to subvert host cell processes in order to promote infection, escape immune detection, and prevent bacterial clearance. Here, we give an overview of pathogenesis while highlighting innovative techniques and methods whose application has significantly advanced our understanding of pathogenesis in recent years.

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pathogenesis. infects the colonic epithelium at the follicle-associated epithelium and near the opening of colonic crypts. Invasion of M cells leads to transcytosis and release of at the basolateral side of the epithelium. can be taken up by macrophages and dendritic cells, which subsequently undergo pyroptosis, stimulating inflammation through the release of IL-1β and IL-18, which recruit neutrophils and activate innate defenses. also efficiently invades the basolateral side of the colonic epithelium from the lamina propria to reach its major replicative niche and the epithelial cell cytosol and propagate infection through cell-to-cell spread.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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T3SS and effectors. () Expression of the T3SS apparatus and its effectors is regulated by a number of environmental factors that, through the transcription factor VirF, control the expression of the transcription factor VirB, which controls the expression of the T3SS apparatus and the first wave of effectors. Upon activation of the T3SS apparatus, MxiE is released from its inhibition and stimulates the transcription of the second wave of effectors. () When the T3SS is closed, first-wave effectors are stored in the bacterial cytoplasm with or without chaperones, while the gatekeeper MxiC and the translocator proteins IpaB and IpaD at the T3SS tip prevent effector secretion. Upon activation of the T3SS, effectors are secreted into the host cell cytosol, and expression of second-wave effectors is mediated by MxiE in complex with IpgC. IM, inner membrane; OM, outer membrane; PM, plasma membrane.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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subversion of host cell survival, integrity, and function. produces numerous effectors that subvert various host cell processes to promote its virulence. Upon invasion of epithelial cells, numerous effectors function to protect the cytosolic replicative niche of by antagonizing host cell death (apoptosis, pyroptosis, and necrosis), promoting host cell integrity, and inhibiting the recruitment of neutrophils, which kill . Conversely, actively promotes host cell death in infected macrophages. For immune cells, mediates B cell death and the inhibition of T cell migration in infected and noninfected cells.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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modulation of antimicrobial defenses and proinflammatory responses. () Numerous effectors have been linked to the evasion of autophagy during cytosolic growth and cell-to-cell spread to foster bacterial survival and propagation. The presence, replication, and spreading of are sensed by the cellular immune surveillance system of the host, which is linked to proinflammatory responses. actively counteracts the cellular proinflammatory response in epithelial cells through inhibition of key signaling pathways () and disruption of the vesicular trafficking pathways ().

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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