Shigella and Enteroinvasive Escherichia Coli

  • Ilia BelotserkovskyEmail author
  • Philippe J. Sansonetti
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 416)


Shigella and enteroinvasive Escherichia coli (EIEC) are gram-negative bacteria responsible for bacillary dysentery (shigellosis) in humans, which is characterized by invasion and inflammatory destruction of the human colonic epithelium. Different EIEC and Shigella subgroups rose independently from commensal E. coli through patho-adaptive evolution that included loss of functional genes interfering with the virulence and/or with the intracellular lifestyle of the bacteria, as well as acquisition of genetic elements harboring virulence genes. Among the latter is the large virulence plasmid encoding for a type three secretion system (T3SS), which enables translocation of virulence proteins (effectors) from the bacterium directly into the host cell cytoplasm. These effectors enable the pathogen to subvert epithelial cell functions, promoting its own uptake, replication in the host cytosol, and dissemination to adjacent cells while concomitantly inhibiting pro-inflammatory cell death. Furthermore, T3SS effectors are directly involved in Shigella manipulation of immune cells causing their dysfunction and promoting cell death. In the current chapter, we first describe the evolution of the enteroinvasive pathovars and then summarize the overall knowledge concerning the pathogenesis of these bacteria, with a particular focus on Shigella flexneri. Subversion of host cell functions in the human gut, both epithelial and immune cells, by different virulence factors is especially highlighted.



The authors wish to thank Mark Anderson and Laurie Pinaud for critical reading of the chapter and proofreading.


  1. Aggarwal P, Uppal B, Ghosh R et al (2016) Multi drug resistance and extended spectrum beta lactamases in clinical isolates of Shigella: a study from New Delhi, India. Travel Med Infect Dis 14:407–413. Scholar
  2. Al-Hasani K, Navarro-Garcia F, Huerta J et al (2009) The immunogenic SigA enterotoxin of S. flexneri 2a binds to HEp-2 cells and induces fodrin redistribution in intoxicated epithelial cells. PLoS ONE 4:e8223. Scholar
  3. Anderson M, Sansonetti PJ, Marteyn BS (2016) Shigella diversity and changing landscape: insights for the twenty-first century. Front Cell Infect Microbiol 6:45. Scholar
  4. Arizmendi O, Picking WD, Picking WL (2016) Macrophage apoptosis triggered by IpaD from S. flexneri. Infect Immun 84:1857–1865. Scholar
  5. Ashida H, Mimuro H, Sasakawa C (2015) Shigella manipulates host immune responses by delivering effector proteins with specific roles. Front Immunol 6:219. Scholar
  6. Barman S, Saha DR, Ramamurthy T, Koley H (2011) Development of a new guinea-pig model of shigellosis. FEMS Immunol Med Microbiol 62:304–314. Scholar
  7. Barzu S, Benjelloun-Touimi Z, Phalipon A et al (1997) Functional analysis of the S. flexneri IpaC invasin by insertional mutagenesis. Infect Immun 65:1599–1605PubMedPubMedCentralGoogle Scholar
  8. Becker SL, Chatigre JK, Gohou J-P et al (2015) Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d’Ivoire. Clin Microbiol Infect 21(591):e1–e10. Scholar
  9. Bensted HJ (1956) Dysentery bacilli-Shigella; a brief historical review. Can J Microbiol 2:163–174CrossRefGoogle Scholar
  10. Bergounioux J, Elisee R, Prunier A-L et al (2012) Calpain activation by the S. flexneri effector VirA regulates key steps in the formation and life of the bacterium’s epithelial niche. Cell Host Microbe 11:240–252. Scholar
  11. Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7:99–109. Scholar
  12. Bhattacharya D, Bhattacharya H, Sayi DS et al (2015) Changing patterns and widening of antibiotic resistance in Shigella spp. over a decade (2000–2011), Andaman Islands. India. Epidemiol Infect 143:470–477. Scholar
  13. Bhattacharya D, Bhattacharya H, Thamizhmani R et al (2014) Shigellosis in Bay of Bengal Islands, India: clinical and seasonal patterns, surveillance of antibiotic susceptibility patterns, and molecular characterization of multidrug-resistant Shigella strains isolated during a 6-year period from 2006 to 2011. Eur J Clin Microbiol Infect Dis 33:157–170. Scholar
  14. Blocker A, Gounon P, Larquet E et al (1999) The tripartite type III secreton of S. flexneri inserts IpaB and IpaC into host membranes. J Cell Biol 147:683–693CrossRefGoogle Scholar
  15. Bougneres L, Girardin SE, Weed SA et al (2004) Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells. J Cell Biol 166:225–235CrossRefGoogle Scholar
  16. Bourdet-Sicard R, Rüdiger M, Jockusch BM et al (1999) Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization. EMBO J 18:5853–5862. Scholar
  17. Bravo V, Puhar A, Sansonetti P et al (2015) Distinct mutations led to inactivation of type 1 fimbriae expression in Shigella spp. PLoS ONE 10:e0121785CrossRefGoogle Scholar
  18. Brinkmann V, Reichard U, Goosmann C et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535CrossRefGoogle Scholar
  19. Brotcke Zumsteg A, Goosmann C, Brinkmann V et al (2014) IcsA is a S. flexneri adhesin regulated by the type III secretion system and required for pathogenesis. Cell Host Microbe 15:435–445. Scholar
  20. Buchrieser C, Glaser P, Rusniok C et al (2000) The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of S. flexneri. Mol Microbiol 38:760–771CrossRefGoogle Scholar
  21. Burnaevskiy N, Fox TG, Plymire DA et al (2013) Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ. Nature 496:106–109. Scholar
  22. Burnaevskiy N, Peng T, Reddick LE et al (2015) Myristoylome profiling reveals a concerted mechanism of ARF GTPase deacylation by the bacterial protease IpaJ. Mol Cell 58:110–122. Scholar
  23. Caboni M, Pedron T, Rossi O et al (2015) An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei. PLoS Pathog 11:e1004749CrossRefGoogle Scholar
  24. Calcuttawala F, Hariharan C, Pazhani GP et al (2015) Activity spectrum of colicins produced by Shigella sonnei and genetic mechanism of colicin resistance in conspecific S. sonnei strains and E. coli. Antimicrob Agents Chemother 59:152–158. Scholar
  25. Campbell-Valois F-X, Sachse M, Sansonetti PJ, Parsot C (2015) Escape of Actively Secreting S. flexneri from ATG8/LC3-positive vacuoles formed during cell-to-cell spread is facilitated by IcsB and VirA. MBio 6:e02567–14. Scholar
  26. Campbell-Valois F-X, Schnupf P, Nigro G et al (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. Scholar
  27. Carayol N, Tran van Nhieu G (2013) Tips and tricks about Shigella invasion of epithelial cells. Curr Opin Microbiol 16:32–37. Scholar
  28. Casalino M, Latella MC, Prosseda G, Colonna B (2003) CadC is the preferential target of a convergent evolution driving enteroinvasive E. coli toward a lysine decarboxylase-defective phenotype. Infect Immun 71:5472–5479CrossRefGoogle Scholar
  29. Casalino M, Latella MC, Prosseda G et al (2005) Molecular evolution of the lysine decarboxylase-defective phenotype in Shigella sonnei. Int J Med Microbiol 294:503–512CrossRefGoogle Scholar
  30. Cohen D, Block C, Green MS et al (1989) Immunoglobulin M, A, and G antibody response to lipopolysaccharide O antigen in symptomatic and asymptomatic Shigella infections. J Clin Microbiol 27:162–167PubMedPubMedCentralGoogle Scholar
  31. Cui X, Yang C, Wang J et al (2015) Antimicrobial resistance of S. flexneri Serotype 1b Isolates in China. PLoS ONE 10:e0129009. Scholar
  32. Day CJ, Tran EN, Semchenko EA et al (2015) Glycan:glycan interactions: high affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells. Proc Natl Acad Sci U S A. Scholar
  33. Day WAJ, Fernandez RE, Maurelli AT (2001) Pathoadaptive mutations that enhance virulence: genetic organization of the cadA regions of Shigella spp. Infect Immun 69:7471–7480. Scholar
  34. Dickenson NE, Zhang L, Epler CR et al (2011) Conformational changes in IpaD from S. flexneri upon binding bile salts provide insight into the second step of type III secretion. Biochemistry 50:172–180. Scholar
  35. Dong N, Zhu Y, Lu Q et al (2012) Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 inactivation to counteract host defenses. Cell 150:1029–1041. Scholar
  36. Doyle M (1989) foodborne bacterial pathogens. CRC PressGoogle Scholar
  37. DuPont HL, Levine MM, Hornick RB, Formal SB (1989) Inoculum size in shigellosis and implications for expected mode of transmission. J Infect Dis 159:1126–1128CrossRefGoogle Scholar
  38. Durand JM, Dagberg B, Uhlin BE, Bjork GR (2000) Transfer RNA modification, temperature and DNA superhelicity have a common target in the regulatory network of the virulence of S. flexneri: the expression of the virF gene. Mol Microbiol 35:924–935CrossRefGoogle Scholar
  39. Edgeworth JD, Spencer J, Phalipon A et al (2002) Cytotoxicity and interleukin-1beta processing following S. flexneri infection of human monocyte-derived dendritic cells. Eur J Immunol 32:1464–1471.;2-GCrossRefPubMedGoogle Scholar
  40. Edwards PR, Ewing WH (1986) Edwards and Ewing’s identification of enterobacteriaceae. Elsevier Publishing CompanyGoogle Scholar
  41. Egile C, Loisel TP, Laurent V et al (1999) Activation of the CDC42 effector N-WASP by the S. flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility. J Cell Biol 146:1319–1332CrossRefGoogle Scholar
  42. Epler CR, Dickenson NE, Olive AJ et al (2009) Liposomes recruit IpaC to the S. flexneri type III secretion apparatus needle as a final step in secretion induction. Infect Immun 77:2754–2761. Scholar
  43. Ewing WH (1949) The relationship of shigella dispar to certain coliform bacteria. J Bacteriol 58:497–500PubMedPubMedCentralGoogle Scholar
  44. Faherty CS, Redman JC, Rasko DA et al (2012) S. flexneri effectors OspE1 and OspE2 mediate induced adherence to the colonic epithelium following bile salts exposure. Mol Microbiol 85:107–121. Scholar
  45. Farfan MJ, Toro CS, Barry EM, Nataro JP (2011) Shigella enterotoxin-2 is a type III effector that participates in Shigella-induced interleukin 8 secretion by epithelial cells. FEMS Immunol Med Microbiol 61:332–339. Scholar
  46. Farmer JJ, Davis BR (1985) H7 antiserum-sorbitol fermentation medium: a single tube screening medium for detecting E. coli O157:H7 associated with hemorrhagic colitis. J Clin Microbiol 22:620–625Google Scholar
  47. Fasano A, Noriega FR, Maneval DRJ et al (1995) Shigella enterotoxin 1: an enterotoxin of S. flexneri 2a active in rabbit small intestine in vivo and in vitro. J Clin Invest 95:2853–2861. Scholar
  48. François M, Le Cabec V, Dupont MA et al (2000) Induction of necrosis in human neutrophils by S. flexneri requires type III secretion, IpaB and IpaC invasins, and actin polymerization. Infect Immun 68:1289–1296CrossRefGoogle Scholar
  49. Franzon VL, Arondel J, Sansonetti PJ (1990) Contribution of superoxide dismutase and catalase activities to S. flexneri pathogenesis. Infect Immun 58:529–535PubMedPubMedCentralGoogle Scholar
  50. Fukumatsu M, Ogawa M, Arakawa S et al (2012) Shigella targets epithelial tricellular junctions and uses a noncanonical clathrin-dependent endocytic pathway to spread between cells. Cell Host Microbe 11:325–336. Scholar
  51. GBD 2013 DALYS and HALE Collaborators, Murray CJL, Barber RM, et al (2015) Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition. Lancet 386:2145–2191. Scholar
  52. GBD (2013b) Mortality and Causes of Death Collaborators (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385:117–171. Scholar
  53. Gorden J, Small PL (1993) Acid resistance in enteric bacteria. Infect Immun 61:364–367PubMedPubMedCentralGoogle Scholar
  54. Guerrero L, Calva JJ, Morrow AL et al (1994) Asymptomatic Shigella infections in a cohort of Mexican children younger than two years of age. Pediatr Infect Dis J 13:597–602CrossRefGoogle Scholar
  55. Haider K, Hossain A, Wanke C et al (1993) Production of mucinase and neuraminidase and binding of Shigella to intestinal mucin. J Diarrhoeal Dis Res 11:88–92PubMedGoogle Scholar
  56. Hancock RE, Diamond G (2000) The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 8:402–410CrossRefGoogle Scholar
  57. Harrington A, Darboe N, Kenjale R et al (2006) Characterization of the interaction of single tryptophan containing mutants of IpaC from S. flexneri with phospholipid membranes. Biochemistry 45:626–636. Scholar
  58. Henderson IR, Czeczulin J, Eslava C et al (1999) Characterization of pic, a secreted protease of S. flexneri and enteroaggregative E. coli. Infect Immun 67:5587–5596PubMedPubMedCentralGoogle Scholar
  59. High N, Mounier J, Prevost MC, Sansonetti PJ (1992) IpaB of S. flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J 11:1991–1999CrossRefGoogle Scholar
  60. Hong M, Payne SM (1997) Effect of mutations in S. flexneri chromosomal and plasmid-encoded lipopolysaccharide genes on invasion and serum resistance. Mol Microbiol 24:779–791CrossRefGoogle Scholar
  61. Hoshino K, Takeuchi O, Kawai T et al (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752PubMedGoogle Scholar
  62. Hume PJ, McGhie EJ, Hayward RD, Koronakis V (2003) The purified Shigella IpaB and Salmonella SipB translocators share biochemical properties and membrane topology. Mol Microbiol 49:425–439CrossRefGoogle Scholar
  63. Ingersoll MA, Moss JE, Weinrauch Y et al (2003) The ShiA protein encoded by the S. flexneri SHI-2 pathogenicity island attenuates inflammation. Cell Microbiol 5:797–807CrossRefGoogle Scholar
  64. Islam D, Bandholtz L, Nilsson J et al (2001) Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7:180–185. Scholar
  65. Islam D, Bardhan PK, Lindberg AA, Christensson B (1995a) Shigella infection induces cellular activation of T and B cells and distinct species-related changes in peripheral blood lymphocyte subsets during the course of the disease. Infect Immun 63:2941–2949PubMedPubMedCentralGoogle Scholar
  66. Islam D, Wretlind B, Ryd M et al (1995b) Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody responses in serum and stool samples in shigellosis. Infect Immun 63:2054–2061PubMedPubMedCentralGoogle Scholar
  67. Ito H, Kido N, Arakawa Y et al (1991) Possible mechanisms underlying the slow lactose fermentation phenotype in Shigella spp. Appl Environ Microbiol 57:2912–2917PubMedPubMedCentralGoogle Scholar
  68. Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327:291–295. Scholar
  69. Izhar M, Nuchamowitz Y, Mirelman D (1982) Adherence of S. flexneri to guinea pig intestinal cells is mediated by a mucosal adhesion. Infect Immun 35:1110–1118PubMedPubMedCentralGoogle Scholar
  70. Janeway CA, Murphy K, Travers P, Walport M (2009) Immunobiologie. De Boeck SupérieurGoogle Scholar
  71. Jin Q, Yuan Z, Xu J et al (2002) Genome sequence of S. flexneri 2a: insights into pathogenicity through comparison with genomes of E. coli K12 and O157. Nucleic Acids Res 30:4432–4441CrossRefGoogle Scholar
  72. Khaghani S, Shamsizadeh A, Nikfar R, Hesami A (2014) S. flexneri: a three-year antimicrobial resistance monitoring of isolates in a Children Hospital, Ahvaz. Iran. Iran J Microbiol 6:225–229PubMedGoogle Scholar
  73. 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. Scholar
  74. Kim HJ, Li H, Collins JJ, Ingber DE (2016) Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci U S A 113:E7–E15. Scholar
  75. Kim M, Ogawa M, Fujita Y et al (2009) Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment. Nature 459:578–582. Scholar
  76. Kobayashi T, Ogawa M, Sanada T et al (2013) The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection. Cell Host Microbe 13:570–583. Scholar
  77. Konradt C, Frigimelica E, Nothelfer K et al (2011) The S. flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism. Cell Host Microbe 9:263–272. Scholar
  78. Kotloff KL, Nataro JP, Blackwelder WC et al (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. Scholar
  79. Kuehl CJ, Dragoi A-M, Agaisse H (2014) The S. flexneri type 3 secretion system is required for tyrosine kinase-dependent protrusion resolution, and vacuole escape during bacterial dissemination. PLoS ONE 9:e112738. Scholar
  80. Kueltzo LA, Osiecki J, Barker J et al (2003) Structure-function analysis of invasion plasmid antigen C (IpaC) from S. flexneri. J Biol Chem 278:2792–2798CrossRefGoogle Scholar
  81. Lafont F, Tran van Nhieu G, Hanada K et al (2002) Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. EMBO J 21:4449–4457CrossRefGoogle Scholar
  82. Lamberti LM, Bourgeois AL, Fischer-Walker CL et al (2014) Estimating diarrheal illness and deaths attributable to Shigellae and enterotoxigenic E. coli among older children, adolescents, and adults in South Asia and Africa. PLoS Negl Trop Dis 8:e2705. Scholar
  83. Lan R, Alles MC, Donohoe K et al (2004) Molecular evolutionary relationships of enteroinvasive E. coli and Shigella spp. Infect Immun 72:5080–5088CrossRefGoogle Scholar
  84. Lanata CF, Fischer-Walker CL, Olascoaga AC et al (2013) Global causes of diarrheal disease mortality in children. PLoS ONE 8:e72788. Scholar
  85. Levine MM, Kotloff KL, Barry EM et al (2007) Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road. Nat Rev Microbiol 5:540–553. Scholar
  86. Lingwood CA (2003) Shiga toxin receptor glycolipid binding. Pathology Utility. Methods Mol Med 73:165–186PubMedGoogle Scholar
  87. Luster AD (2002) The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol 14:129–135CrossRefGoogle Scholar
  88. Mani S, Wierzba T, Walker RI (2016) Status of vaccine research and development for Shigella. Vaccine 34:2887–2894. Scholar
  89. Marteyn B, West NP, Browning DF et al (2010) Modulation of Shigella virulence in response to available oxygen in vivo. Nature 465:355–358. Scholar
  90. Martins dos Santos V, Muller M, de Vos WM (2010) Systems biology of the gut: the interplay of food, microbiota and host at the mucosal interface. Curr Opin Biotechnol 21:539–550. Scholar
  91. Maurelli AT, Fernandez RE, Bloch CA et al (1998) “Black holes” and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive E. coli. Proc Natl Acad Sci U S A 95:3943–3948CrossRefGoogle Scholar
  92. Maurelli AT, Sansonetti PJ (1988) Identification of a chromosomal gene controlling temperature-regulated expression of Shigella virulence. Proc Natl Acad Sci U S A 85:2820–2824CrossRefGoogle Scholar
  93. McCord JM, Fridovich I (1978) The biology and pathology of oxygen radicals. Ann Intern Med 89:122–127CrossRefGoogle Scholar
  94. Mellouk N, Weiner A, Aulner N et al (2014) Shigella subverts the host recycling compartment to rupture its vacuole. Cell Host Microbe 16:517–530. Scholar
  95. Mostowy S, Bonazzi M, Hamon MA et al (2010) Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 8:433–444. Scholar
  96. Mounier J, Boncompain G, Senerovic L et al (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. Scholar
  97. Mounier J, Vasselon T, Hellio R et al (1992) S. flexneri enters human colonic Caco-2 epithelial cells through the basolateral pole. Infect Immun 60:237–248PubMedPubMedCentralGoogle Scholar
  98. Murray CJL, Vos T, Lozano R et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 380:2197–2223. Scholar
  99. Nataro JP, Seriwatana J, Fasano A et al (1995) Identification and cloning of a novel plasmid-encoded enterotoxin of enteroinvasive E. coli and Shigella strains. Infect Immun 63:4721–4728PubMedPubMedCentralGoogle Scholar
  100. Niebuhr K, Jouihri N, Allaoui A et al (2000) IpgD, a protein secreted by the type III secretion machinery of S. flexneri, is chaperoned by IpgE and implicated in entry focus formation. Mol Microbiol 38:8–19CrossRefGoogle Scholar
  101. Nothelfer K, Arena ET, Pinaud L et al (2014) B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection. J Exp Med 211:1215–1229. Scholar
  102. Ogawa M, Handa Y, Ashida H et al (2008) The versatility of Shigella effectors. Nat Rev Microbiol 6:11–16. Scholar
  103. Ogawa M, Yoshimori T, Suzuki T et al (2005) Escape of intracellular Shigella from autophagy. Science 307:727–731. Scholar
  104. Paciello I, Silipo A, Lembo-Fazio L et al (2013) Intracellular Shigella remodels its LPS to dampen the innate immune recognition and evade inflammasome activation. Proc Natl Acad Sci U S A 110:E4345–E4354. Scholar
  105. Parsot C (2009) Shigella type III secretion effectors: how, where, when, for what purposes? Curr Opin Microbiol 12:110–116. Scholar
  106. Parsot C (2005) Shigella spp. and enteroinvasive E. coli pathogenicity factors. FEMS Microbiol Lett 252:11–18. Scholar
  107. Patel SK, Dotson J, Allen KP, Fleckenstein JM (2004) Identification and molecular characterization of EatA, an autotransporter protein of enterotoxigenic E. coli. Infect Immun 72:1786–1794CrossRefGoogle Scholar
  108. Payne SM, Wyckoff EE, Murphy ER et al (2006) Iron and pathogenesis of Shigella: iron acquisition in the intracellular environment. Biometals 19:173–180. Scholar
  109. Pendaries C, Tronchere H, Arbibe L et al (2006) PtdIns5P activates the host cell PI3-kinase/Akt pathway during S. flexneri infection. EMBO J 25:1024–1034. Scholar
  110. Pettengill EA, Pettengill JB, Binet R (2015) Phylogenetic analyses of Shigella and Enteroinvasive E. coli for the identification of markers: whole-genome comparative analysis does not support distinct genera designation. Front Microbiol 6:1573. Scholar
  111. Phalipon A, Kaufmann M, Michetti P et al (1995) Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of S. flexneri lipopolysaccharide protects against murine experimental shigellosis. J Exp Med 182:769–778CrossRefGoogle Scholar
  112. Phalipon A, Sansonetti PJ (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. Scholar
  113. Poltorak A, He X, Smirnova I et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088CrossRefGoogle Scholar
  114. Poramathikul K, Bodhidatta L, Chiek S et al (2016) Multidrug-Resistant Shigella infections in patients with diarrhea, Cambodia, 2014-2015. Emerg Infect Dis 22:1640–1643. Scholar
  115. Porter ME, Dorman CJ (1994) A role for H-NS in the thermo-osmotic regulation of virulence gene expression in S. flexneri. J Bacteriol 176:4187–4191. Scholar
  116. Prunier A-L, Schuch R, Fernandez RE et al (2007) nadA and nadB of S. flexneri 5a are antivirulence loci responsible for the synthesis of quinolinate, a small molecule inhibitor of Shigella pathogenicity. Microbiology 153:2363–2372. Scholar
  117. Puhar A, Tronchere H, Payrastre B et al (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. Scholar
  118. Pupo GM, Lan R, Reeves PR (2000) Multiple independent origins of Shigella clones of E. coli and convergent evolution of many of their characteristics. Proc Natl Acad Sci U S A 97:10567–10572CrossRefGoogle Scholar
  119. Qadri MH, Ai-Gamdi MA, Al-Harfi RA (1995) Asymptomatic salmonella, Shigella and intestinal parasites among primary school children in the eastern province. J Family Community Med 2:36–40PubMedPubMedCentralGoogle Scholar
  120. Ramos HC, Rumbo M, Sirard J-C (2004) Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends Microbiol 12:509–517. Scholar
  121. Raqib R, Ekberg C, Sharkar P et al (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 70:3199–3207CrossRefGoogle Scholar
  122. Raqib R, Lindberg AA, Björk L et al (1995) Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1 (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors at the local site during the acute phase of Shigella infection. Infect Immun 63:3079–3087PubMedPubMedCentralGoogle Scholar
  123. Raqib R, Mia SM, Qadri F et al (2000) Innate immune responses in children and adults with Shigellosis. Infect Immun 68:3620–3629CrossRefGoogle Scholar
  124. Romero S, Grompone G, Carayol N et al (2011) ATP-mediated Erk1/2 activation stimulates bacterial capture by filopodia, which precedes Shigella invasion of epithelial cells. Cell Host Microbe 9:508–519. Scholar
  125. Sadeghabadi AF, Ajami A, Fadaei R et al (2014) Widespread antibiotic resistance of diarrheagenic E. coli and Shigella species. J Res Med Sci 19:S51–S55PubMedPubMedCentralGoogle Scholar
  126. Sakellaris H, Hannink NK, Rajakumar K et al (2000) Curli loci of Shigella spp. Infect Immun 68:3780–3783CrossRefGoogle Scholar
  127. Salgado-Pabón W, Celli S, Arena ET et al (2013) Shigella impairs T lymphocyte dynamics in vivo. Proc Natl Acad Sci U S A 110:4458–4463. Scholar
  128. Sansonetti PJ (2004) War and peace at mucosal surfaces. Nat Rev Immunol 4:953–964. Scholar
  129. Sansonetti PJ, D’Hauteville H, Ecobichon C, Pourcel C (1983) Molecular comparison of virulence plasmids in Shigella and enteroinvasive E. coli. Ann Microbiol (Paris) 134A:295–318Google Scholar
  130. Sansonetti PJ, Tran Van Nhieu G, Egile C (1999) Rupture of the intestinal epithelial barrier and mucosal invasion by S. flexneri. Clin Infect Dis 28:466–475. Scholar
  131. 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. Scholar
  132. Sellge G, Magalhaes JG, Konradt C et al (2010) Th17 cells are the dominant T cell subtype primed by S. flexneri mediating protective immunity. J Immunol 184:2076–2085. Scholar
  133. Senerovic L, Tsunoda SP, Goosmann C et al (2012) Spontaneous formation of IpaB ion channels in host cell membranes reveals how Shigella induces pyroptosis in macrophages. Cell Death Dis 3:e384. Scholar
  134. Shim D-H, Suzuki T, Chang S-Y et al (2007) New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies. J Immunol 178:2476–2482CrossRefGoogle Scholar
  135. Skoudy A, Mounier J, Aruffo A et al (2000) CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells. Cell Microbiol 2:19–33CrossRefGoogle Scholar
  136. Sperandio B, Fischer N, Joncquel Chevalier-Curt M et al (2013) Virulent S. flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells. Infect Immun 81:3632–3643. Scholar
  137. Sperandio B, Regnault B, Guo J et al (2008) Virulent S. flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. J Exp Med 205:1121–1132. Scholar
  138. Sudha PS, Devaraj H, Devaraj N (2001) Adherence of Shigella dysenteriae 1 to human colonic mucin. Curr Microbiol 42:381–387. Scholar
  139. Suzuki S, Mimuro H, Kim M et al (2014) Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages. Proc Natl Acad Sci U S A 111:E4254–E4263. Scholar
  140. Tesh VL (2010) Induction of apoptosis by Shiga toxins. Future Microbiol 5:431–453. Scholar
  141. 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. Scholar
  142. 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. Scholar
  143. Tran van Nhieu G, Kai Liu B, Zhang J et al (2013) Actin-based confinement of calcium responses during Shigella invasion. Nat Commun 4:1567. Scholar
  144. van den Broek JM, Roy SK, Khan WA et al (2005) Risk factors for mortality due to shigellosis: a case-control study among severely-malnourished children in Bangladesh. J Health Popul Nutr 23:259–265PubMedGoogle Scholar
  145. van der Goot FG, Tran van Nhieu G, Allaoui A et al (2004) Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism. J Biol Chem 279:47792–47798CrossRefGoogle Scholar
  146. Watarai M, Funato S, Sasakawa C (1996) Interaction of Ipa proteins of S. flexneri with alpha5beta1 integrin promotes entry of the bacteria into mammalian cells. J Exp Med 183:991–999CrossRefGoogle Scholar
  147. Wei J, Goldberg MB, Burland V et al (2003) Complete genome sequence and comparative genomics of S. flexneri serotype 2a strain 2457T. Infect Immun 71:2775–2786CrossRefGoogle Scholar
  148. Weinrauch Y, Drujan D, Shapiro SD et al (2002) Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:91–94. Scholar
  149. West NP, Sansonetti P, Mounier J et al (2005) Optimization of virulence functions through glucosylation of Shigella LPS. Science 307:1313–1317. Scholar
  150. Yang C, Li P, Zhang X et al (2016) Molecular characterization and analysis of high-level multidrug-resistance of S. flexneri serotype 4 s strains from China. Sci Rep 6:29124. Scholar
  151. Yang F, Yang J, Zhang X et al (2005) Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res 33:6445–6458. Scholar
  152. Yoshida S, Katayama E, Kuwae A et al (2002) Shigella deliver an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization. EMBO J 21:2923–2935. Scholar
  153. Zhang Y-G, Sun J (2016) Study bacteria-host interactions using intestinal organoids. Methods Mol Biol. Scholar
  154. Zhang Z, Jin L, Champion G et al (2001) Shigella infection in a SCID mouse-human intestinal xenograft model: role for neutrophils in containing bacterial dissemination in human intestine. Infect Immun 69:3240–3247. Scholar
  155. Zychlinsky A, Prevost MC, Sansonetti PJ (1992) S. flexneri induces apoptosis in infected macrophages. Nature 358:167–169. Scholar
  156. Zychlinsky A, Thirumalai K, Arondel J et al (1996) In vivo apoptosis in S. flexneri infections. Infect Immun 64:5357–5365PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Unité de Pathogénie Microbienne MoléculaireInstitut PasteurParisFrance
  2. 2.Microbiologie et Maladies Infectieuses, Collège de FranceParisFrance

Personalised recommendations