Review

Pathogenesis of adherent–invasive Escherichia coli

Emma J Smith

Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

Search for more papers by this author

Aoife P Thompson

Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

Search for more papers by this author

Adam O‘Driscoll

Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

Search for more papers by this author

David J Clarke

* Author for correspondence

Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.

Search for more papers by this author

Email the corresponding author at david.clarke@ucc.ie

Published Online:24 Sep 2013https://doi.org/10.2217/fmb.13.94

View article

Abstract

The etiology of Crohn‘s disease (CD) is complex and involves both host susceptibility factors (i.e., the presence of particular genetic alleles) and environmental factors, including bacteria. In this regard, adherent–invasive Escherichia coli (AIEC), have recently emerged as an exciting potential etiological agent of CD. AIEC are distinguished from commensal strains of E. coli through their ability to adhere to and invade epithelial cells and replicate in macrophages. Recent molecular analyses have identified genes required for both invasion of epithelial cells and replication in the macrophage. However, these genetic studies, in combination with recent genome sequencing projects, have revealed that the pathogenesis of this group of bacteria cannot be explained by the presence of AIEC-specific genes. In this article, we review the role of AIEC as a pathobiont in the pathology of CD. We also describe the emerging link between AIEC and autophagy, and we propose a model for AIEC pathogenesis.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence and environmental influences. Gastroenterology126(6),1504–1517 (2004).Crossref, Medline, Google Scholar
2 Craven M, Egan CE, Dowd SE et al. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn‘s disease. PLoS ONE7(7),e41594 (2012).Crossref, Medline, CAS, Google Scholar
3 Strober W. Adherent–invasive E. coli in Crohn disease: bacterial “agent provocateur”. J. Clin. Invest.121(3),841–844 (2011).Crossref, Medline, CAS, Google Scholar
4 Eckburg PB, Relman DA. The role of microbes in Crohn‘s disease. Clin. Infect. Dis.44(2),256–262 (2007).Crossref, Medline, CAS, Google Scholar
5 Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J. Clin. Invest.117(3),514–521 (2007).Crossref, Medline, CAS, Google Scholar
6 Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature448(7152),427–434 (2007).Crossref, Medline, CAS, Google Scholar
7 Rivas MA, Beaudoin M, Gardet A et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet.43(11),1066–1073 (2011).Crossref, Medline, CAS, Google Scholar
8 Rioux JD, Xavier RJ, Taylor KD et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet.39(5),596–604 (2007).Crossref, Medline, CAS, Google Scholar
9 Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn‘s disease. Nature411(6837),599–603 (2001).Crossref, Medline, CAS, Google Scholar
10 Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn‘s disease. Nature411(6837),603–606 (2001).Crossref, Medline, CAS, Google Scholar
11 Inohara N, Ogura Y, Fontalba A et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn‘s disease. J. Biol. Chem.278(8),5509–5512 (2003).Crossref, Medline, CAS, Google Scholar
12 Vignal C, Singer E, Peyrin-Biroulet L, Desreumaux P, Chamaillard M. How NOD2 mutations predispose to Crohn‘s disease? Microbes Infect.9(5),658–663 (2007).Crossref, Medline, CAS, Google Scholar
13 Barreau F, Madre C, Meinzer U et al. Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer‘s patches. Gut59(2),207–217 (2010).Crossref, Medline, CAS, Google Scholar
14 Lapaquette P, Glasser AL, Huett A, Xavier RJ, Darfeuille-Michaud A. Crohn‘s disease-associated adherent–invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell. Microbiol.12(1),99–113 (2010).Crossref, Medline, CAS, Google Scholar
15 Cooney R, Baker J, Brain O et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med.16(1),90–97 (2010).Crossref, Medline, CAS, Google Scholar
16 Meconi S, Vercellone A, Levillain F et al. Adherent–invasive Escherichia coli isolated from Crohn‘s disease patients induce granulomas in vitro. Cell. Microbiol.9(5),1252–1261 (2007).Crossref, Medline, CAS, Google Scholar
17 Arnold GL, Beaves MR, Pryjdun VO, Mook WJ. Preliminary study of ciprofloxacin in active Crohn‘s disease. Inflamm. Bowel Dis.8(1),10–15 (2002).Crossref, Medline, Google Scholar
18 Gionchetti P, Rizzello F, Morselli C, Romagnoli R, Campieri M. Management of inflammatory bowel disease: does rifaximin offer any promise? Chemotherapy51(Suppl. 1),S96–S102 (2005).Crossref, Medline, CAS, Google Scholar
19 Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu. Rev. Immunol.20,495–549 (2002).Crossref, Medline, CAS, Google Scholar
20 Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl Acad. Sci. USA104(34),13780–13785 (2007).Crossref, Medline, CAS, Google Scholar
21 Chiodini RJ, Van Kruiningen HJ, Thayer WR, Merkal RS, Coutu JA. Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn‘s disease. Dig. Dis. Sci.29(12),1073–1079 (1984).Crossref, Medline, CAS, Google Scholar
22 Sartor RB. Does Mycobacterium avium subspecies paratuberculosis cause Crohn‘s disease? Gut54(7),896–898 (2005).Crossref, Medline, Google Scholar
23 Chacon O, Bermudez LE, Barletta RG. Johne‘s disease, inflammatory bowel disease, and Mycobacterium paratuberculosis. Annu. Rev. Microbiol.58,329–363 (2004).Crossref, Medline, CAS, Google Scholar
24 Millar D, Ford J, Sanderson J et al. IS900 PCR to detect Mycobacterium paratuberculosis in retail supplies of whole pasteurized cows‘ milk in England and Wales. Appl. Environ. Microbiol.62(9),3446–3452 (1996).Crossref, Medline, CAS, Google Scholar
25 Selby W, Pavli P, Crotty B et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn‘s disease. Gastroenterology132(7),2313–2319 (2007).Crossref, Medline, CAS, Google Scholar
26 Autschbach F, Eisold S, Hinz U et al. High prevalence of Mycobacterium avium subspecies paratuberculosis IS900 DNA in gut tissues from individuals with Crohn‘s disease. Gut54(7),944–949 (2005).Crossref, Medline, CAS, Google Scholar
27 Bull TJ, Mcminn EJ, Sidi-Boumedine K et al. Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn‘s disease. J. Clin. Microbiol.41(7),2915–2923 (2003).Crossref, Medline, CAS, Google Scholar
28 Naser SA, Ghobrial G, Romero C, Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn‘s disease. Lancet364(9439),1039–1044 (2004).Crossref, Medline, Google Scholar
29 Sartor RB. Mechanisms of disease: pathogenesis of Crohn‘s disease and ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol.3(7),390–407 (2006).Crossref, Medline, CAS, Google Scholar
30 Rhodes JM. The role of Escherichia coli in inflammatory bowel disease. Gut56(5),610–612 (2007).Crossref, Medline, CAS, Google Scholar
31 Rolhion N, Darfeuille-Michaud A. Adherent–invasive Escherichia coli in inflammatory bowel disease. Inflamm. Bowel Dis.13(10),1277–1283 (2007).Crossref, Medline, Google Scholar
32 Martin HM, Campbell BJ, Hart CA et al. Enhanced Escherichia coli adherence and invasion in Crohn‘s disease and colon cancer. Gastroenterology127(1),80–93 (2004).Crossref, Medline, CAS, Google Scholar
33 de Souza HL, de Carvalho VR, Romeiro FG, Sassaki LY, Keller R, Rodrigues J. Mucosa-associated but not luminal Escherichia coli is augmented in Crohn‘s disease and ulcerative colitis. Gut Pathog.4(1),21 (2012).Crossref, Medline, CAS, Google Scholar
34 Ryan P, Kelly RG, Lee G et al. Bacterial DNA within granulomas of patients with Crohn‘s disease – detection by laser capture microdissection and PCR. Am. J.Gastroenterol.99(8),1539–1543 (2004).Crossref, Medline, CAS, Google Scholar
35 Schultsz C, Van Den Berg FM, Ten Kate FW, Tytgat GN, Dankert J. The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology117(5),1089–1097 (1999).Crossref, Medline, CAS, Google Scholar
36 Darfeuille-Michaud A, Neut C, Barnich N et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn‘s disease. Gastroenterology115,1405–1413 (1998).▪▪ The high prevelance of adherent–invasive Escherichia coli (AIEC) in the gut of Crohn‘s disease (CD) patients established AIEC as a potential etiological agent for CD.Crossref, Medline, CAS, Google Scholar
37 Darfeuille-Michaud A, Boudeau J, Bulois P et al. High prevalence of adherent–invasive Escherichia coli associated with ileal mucosa in Crohn‘s disease. Gastroenterology127,412–421 (2004).▪▪ The high prevelance of AIEC in the gut of CD patients established AIEC as a potential etiological agent for CD.Crossref, Medline, Google Scholar
38 Mylonaki M, Rayment NB, Rampton DS, Hudspith BN, Brostoff J. Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease. Inflamm. Bowel Dis.11(5),481–487 (2005).Crossref, Medline, Google Scholar
39 Landers CJ, Cohavy O, Misra R et al. Selected loss of tolerance evidenced by Crohn‘s disease-associated immune responses to auto- and microbial antigens. Gastroenterology123(3),689–699 (2002).Crossref, Medline, CAS, Google Scholar
40 Mei L, Targan SR, Landers CJ et al. Familial expression of anti-Escherichia coli outer membrane porin C in relatives of patients with Crohn‘s disease. Gastroenterology130(4),1078–1085 (2006).Crossref, Medline, CAS, Google Scholar
41 Martin HM, Campbell BJ, Hart CA et al. Enhanced Escherichia coli adherence and invasion in Crohn‘s disease and colon cancer. Gastroenterology127(1),80–93 (2004).Crossref, Medline, CAS, Google Scholar
42 Manchester AC, Hill S, Sabatino B et al. Association between granulomatous colitis in French Bulldogs and invasive Escherichia coli and response to fluoroquinolone antimicrobials. J. Vet. Intern. Med.27(1),56–61 (2013).Crossref, Medline, CAS, Google Scholar
43 Dogan B, Klaessig S, Rishniw M et al. Adherent and invasive Escherichia coli are associated with persistent bovine mastitis. Vet. Microbiol.116(4),270–282 (2006).Crossref, Medline, CAS, Google Scholar
44 Martinez-Medina M, Mora A, Blanco M et al. Similarity and divergence among adherent–invasive Escherichia coli and extraintestinal pathogenic E. coli strains. J. Clin. Microbiol.47(12),3968–3979 (2009).Crossref, Medline, CAS, Google Scholar
45 Martinez-Medina M, Aldeguer X, Lopez-Siles M et al. Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent–invasive E. coli (AIEC) in Crohn‘s disease. Inflamm. Bowel Dis.15(6),872–882 (2009).Crossref, Medline, Google Scholar
46 Kotlowski R, Bernstein CN, Sepehri S, Krause DO. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut56(5),669–675 (2007).Crossref, Medline, CAS, Google Scholar
47 Schippa S, Iebba V, Totino V et al. A potential role of Escherichia coli pathobionts in the pathogenesis of pediatric inflammatory bowel disease. Can. J. Microbiol.58(4),426–432 (2012).Crossref, Medline, CAS, Google Scholar
48 Carlos C, Pires MM, Stoppe NC et al.Escherichia coli phylogenetic group determination and its application in the identification of the major animal source of fecal contamination. BMC Microbiol.10,161 (2010).Crossref, Medline, Google Scholar
49 White AP, Sibley KA, Sibley CD et al. Intergenic sequence comparison of Escherichia coli isolates reveals lifestyle adaptations but not host specificity. Appl. Environ. Microbiol.77(21),7620–7632 (2011).Crossref, Medline, CAS, Google Scholar
50 Bingen E, Picard B, Brahimi N et al. Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulent B2 group strains. J. Infect. Dis.177(3),642–650 (1998).Crossref, Medline, CAS, Google Scholar
51 Johnson JR, Delavari P, Kuskowski M, Stell AL. Phylogenetic distribution of extraintestinal virulence-associated traits in Escherichia coli. J. Infect. Dis.183(1),78–88 (2001).Crossref, Medline, CAS, Google Scholar
52 Nash JH, Villegas A, Kropinski AM et al. Genome sequence of adherent–invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes. BMC Genomics.11,667 (2010).Crossref, Medline, Google Scholar
53 Clarke DJ, Chaudhuri RR, Martin HM et al. Complete genome sequence of the Crohn‘s disease-associated adherent–invasive Escherichia coli strain HM605. J. Bacteriol.193(17),4540 (2011).Crossref, Medline, CAS, Google Scholar
54 Krause DO, Little AC, Dowd SE, Bernstein CN. Complete genome sequence of adherent invasive Escherichia coli UM146 isolated from ileal Crohn‘s disease biopsy tissue. J. Bacteriol.193(2),583 (2011).Crossref, Medline, CAS, Google Scholar
55 Kagnoff MF, Eckmann L. Epithelial cells as sensors for microbial infection. J. Clin. Invest.100(1),6–10 (1997).Crossref, Medline, CAS, Google Scholar
56 Knight P, Campbell BJ, Rhodes JM. Host–bacteria interaction in inflammatory bowel disease. Br. Med. Bull.88(1),95–113 (2008).Crossref, Medline, CAS, Google Scholar
57 Garside P, Millington O, Smith KM. The anatomy of mucosal immune responses. Ann. N. Y. Acad. Sci.1029,9–15 (2004).Crossref, Medline, CAS, Google Scholar
58 Miller H, Zhang J, Kuolee R, Patel GB, Chen W. Intestinal M cells: the fallible sentinels? World J. Gastroenterol.13(10),1477–1486 (2007).Crossref, Medline, CAS, Google Scholar
59 Sasaki M, Sitaraman SV, Babbin BA et al. Invasive Escherichia coli are a feature of Crohn‘s disease. Lab. Invest.87(10),1042–1054 (2007).Crossref, Medline, CAS, Google Scholar
60 Wine E, Ossa JC, Gray-Owen SD, Sherman PM. Adherent–invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia. BMC Microbiol.9,180 (2009).Crossref, Medline, Google Scholar
61 Fujimura Y, Kamoi R, Iida M. Pathogenesis of aphthoid ulcers in Crohn‘s disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. Gut38(5),724–732 (1996).Crossref, Medline, CAS, Google Scholar
62 Hase K, Kawano K, Nochi T et al. Uptake through glycoprotein 2 of FimH(⁺) bacteria by M cells initiates mucosal immune response. Nature462(7270),226–230 (2009).Crossref, Medline, CAS, Google Scholar
63 Chassaing B, Darfeuille-Michaud A. The interaction of Crohn‘s disease-associated Escherichia coli to Peyer‘s patches of the intestinal mucosa involves long polar fimbriae. Med. Sci.27(6–7),572–573 (2011).Google Scholar
64 Chassaing B, Rolhion N, de Vallée A et al. Crohn disease – associated adherent–invasive E. coli bacteria target mouse and human Peyer‘s patches via long polar fimbriae. J. Clin. Invest.121(3),966–975 (2011).▪ Identified long polar fimbriae as an important factor in the ability of AIEC to interact with Peyer‘s patches.Crossref, Medline, CAS, Google Scholar
65 Baumler AJ, Tsolis RM, Heffron F. The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine Peyer‘s patches. Proc. Natl Acad. Sci. USA93(1),279–283 (1996).Crossref, Medline, CAS, Google Scholar
66 Barnich N, Darfeuille-Michaud A. Role of bacteria in the etiopathogenesis of inflammatory bowel disease. World J. Gastroenterol.13(42),5571–5576 (2007).Crossref, Medline, CAS, Google Scholar
67 Barnich N, Darfeuille-Michaud A. Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and inflammation by adherent–invasive E. coli. Virulence1(4),281–282 (2010).Crossref, Medline, Google Scholar
68 Dreux N, Denizot J, Martinez-Medina M et al. Point mutations in FimH adhesin of Crohn‘s disease-associated adherent–invasive Escherichia coli enhance intestinal inflammatory response. PLoS Pathog.9(1),e1003141 (2013).▪▪ Reported that AIEC strains predominantly express FimH with amino acid mutations that confer a significantly higher ability to adhere to CEACAM-expressing T84 intestinal epithelial cells on the bacteria.Crossref, Medline, CAS, Google Scholar
69 Barnich N, Carvalho FA, Glasser AL et al. CEACAM6 acts as a receptor for adherent–invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J. Clin. Invest.117(6),1566–1574 (2007).▪ Reported that CEACAM6 acts as a receptor for AIEC and is abnormally expressed by ileal epithelial cells in CD patients.Crossref, Medline, CAS, Google Scholar
70 Denizot J, Sivignon A, Barreau F et al. Adherent–invasive Escherichia coli induce claudin-2 expression and barrier defect in CEABAC10 mice and Crohn‘s disease patients. Inflamm. Bowel Dis.18(2),294–304 (2012).Crossref, Medline, Google Scholar
71 Vazeille E, Bringer MA, Gardarin A et al. Role of meprins to protect ileal mucosa of Crohn‘s disease patients from colonization by adherent–invasive E. coli. PLoS ONE6(6),e21199 (2011).Crossref, Medline, CAS, Google Scholar
72 Rolhion N, Barnich N, Claret L, Darfeuille-Michaud A. Strong decrease in invasive ability and outer membrane vesicle release in Crohn‘s disease-associated adherent–invasive Escherichia coli strain LF82 with the yfgL gene deleted. J. Bacteriol.187(7),2286–2296 (2005).Crossref, Medline, CAS, Google Scholar
73 Eggert US, Ruiz N, Falcone BV et al. Genetic basis for activity differences between vancomycin and glycolipid derivatives of vancomycin. Science294(5541),361–364 (2001).Crossref, Medline, CAS, Google Scholar
74 Rolhion N, Hofman P, Darfeuille-Michaud A. The endoplasmic reticulum stress response chaperone: Gp96, a host receptor for Crohn disease-associated adherent–invasive Escherichia coli. Gut Microbes2(2),115–119 (2011).Crossref, Medline, Google Scholar
75 Nickerson KP, McDonald C. Crohn‘s disease-associated adherent–invasive Escherichia coli adhesion is enhanced by exposure to the ubiquitous dietary polysaccharide maltodextrin. PLoS ONE7(12),e52132 (2012).▪ Suggests a mechanism by which western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to CD susceptibility.Crossref, Medline, CAS, Google Scholar
76 Roberts CL, Keita AV, Duncan SH et al. Translocation of Crohn‘s disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut59(10),1331–1339 (2010).Crossref, Medline, Google Scholar
77 Martinez-Medina M, Denizot J, Dreux N et al. Western diet induces dysbiosis with increased E. coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut doi:10.1136/gutjnl-2012–304119 (2013) (Epub ahead of print).Medline, Google Scholar
78 MacDonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science307(5717),1920–1925 (2005).Crossref, Medline, CAS, Google Scholar
79 Glasser AL, Boudeau J, Barnich N et al. Adherent invasive Escherichia coli strains from patients with Crohn‘s disease survive and replicate within macrophages without inducing host cell death. Infect. Immun.69,5529–5537 (2001).▪▪ The first study to demonstrate that AIEC strains are able to survive and replicate within macrophages.Crossref, Medline, CAS, Google Scholar
80 Bringer MA, Glasser AL, Tung CH, Meresse S, Darfeuille-Michaud A. The Crohn‘s disease-associated adherent–invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages. Cell. Microbiol.8(3),471–484 (2006).▪▪ Found that LF82-containing phagosomes mature into active phagolysosomes where bacteria are exposed to low pH and to the degradative activity of cathepsin D.Crossref, Medline, CAS, Google Scholar
81 Alpuche-Aranda CM, Racoosin EL, Swanson JA, Miller SI. Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes. J. Exp. Med.179(2),601–608 (1994).Crossref, Medline, CAS, Google Scholar
82 Buchmeier NA, Heffron F. Inhibition of macrophage phagosome–lysosome fusion by Salmonella typhimurium. Infect. Immun.59(7),2232–2238 (1991).Crossref, Medline, CAS, Google Scholar
83 Hashim S, Mukherjee K, Raje M, Basu SK, Mukhopadhyay A. Live Salmonella modulate expression of rab proteins to persist in a specialized compartment and escape transport to lysosomes. J. Biol. Chem.275(21),16281–16288 (2000).Crossref, Medline, CAS, Google Scholar
84 Bringer MA, Barnich N, Glasser AL, Bardot O, Darfeuille-Michaud A. HtrA stress protein is involved in intramacrophagic replication of adherent and invasive Escherichia coli strain LF82 isolated from a patient with Crohn‘s disease. Infect. Immun.73(2),712–721 (2005).Crossref, Medline, CAS, Google Scholar
85 Baumler AJ, Kusters JG, Stojiljkovic I, Heffron F. Salmonella typhimurium loci involved in survival within macrophages. Infect. Immun.62(5),1623–1630 (1994).Crossref, Medline, CAS, Google Scholar
86 Eriksson S, Lucchini S, Thompson A, Rhen M, Hinton JC. Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica.Mol. Microbiol.47(1),103–118 (2003).Crossref, Medline, CAS, Google Scholar
87 Pedersen LL, Radulic M, Doric M, Abu Kwaik Y. HtrA homologue of Legionella pneumophila: an indispensable element for intracellular infection of mammalian but not protozoan cells. Infect. Immun.69(4),2569–2579 (2001).Crossref, Medline, CAS, Google Scholar
88 Elzer PH, Phillips RW, Robertson GT, Roop RM 2nd. The HtrA stress response protease contributes to resistance of Brucella abortus to killing by murine phagocytes. Infect. Immun.64(11),4838–4841 (1996).Crossref, Medline, CAS, Google Scholar
89 Heras B, Shouldice SR, Totsika M, Scanlon MJ, Schembri MA, Martin JL. Dsb proteins and bacterial pathogenicity. Nat. Rev. Microbiol.7(3),215–225 (2009).Crossref, Medline, CAS, Google Scholar
90 Peek JA, Taylor RK. Characterization of a periplasmic thiol:disulfide interchange protein required for the functional maturation of secreted virulence factors of Vibrio cholerae. Proc. Natl Acad. Sci. USA89(13),6210–6214 (1992).Crossref, Medline, CAS, Google Scholar
91 Okamoto K, Baba T, Yamanaka H, Akashi N, Fujii Y. Disulfide bond formation and secretion of Escherichia coli heat-stable enterotoxin II. J. Bacteriol.177(16),4579–4586 (1995).Crossref, Medline, CAS, Google Scholar
92 Dailey FE, Berg HC. Mutants in disulfide bond formation that disrupt flagellar assembly in Escherichia coli. Proc. Natl Acad. Sci. USA90(3),1043–1047 (1993).Crossref, Medline, CAS, Google Scholar
93 Donnenberg MS, Zhang HZ, Stone KD. Biogenesis of the bundle-forming pilus of enteropathogenic Escherichia coli: reconstitution of fimbriae in recombinant E. coli and role of DsbA in pilin stability – a review. Gene192(1),33–38 (1997).Crossref, Medline, CAS, Google Scholar
94 Jacob-Dubuisson F, Pinkner J, Xu Z, Striker R, Padmanhaban A, Hultgren SJ. PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of DsbA. Proc. Natl Acad. Sci. USA91(24),11552–11556 (1994).Crossref, Medline, CAS, Google Scholar
95 Bringer MA, Rolhion N, Glasser AL, Darfeuille-Michaud A. The oxidoreductase DsbA plays a key role in the ability of the Crohn‘s disease-associated adherent–invasive Escherichia coli strain LF82 to resist macrophage killing. J. Bacteriol.189(13),4860–4871 (2007).Crossref, Medline, CAS, Google Scholar
96 Yu J, Oragui EE, Stephens A, Kroll JS, Venkatesan MM. Inactivation of DsbA alters the behaviour of Shigella flexneri towards murine and human-derived macrophage-like cells. FEMS Microbiol. Lett.204(1),81–88 (2001).Crossref, Medline, CAS, Google Scholar
97 Simonsen KT, Nielsen G, Bjerrum JV, Kruse T, Kallipolitis BH, Moller-Jensen J. A role for the RNA chaperone Hfq in controlling adherent–invasive Escherichia coli colonization and virulence. PLoS ONE6(1),e16387 (2011).Crossref, Medline, CAS, Google Scholar
98 Vogel J, Luisi BF. Hfq and its constellation of RNA. Nat. Rev. Microbiol.9(8),578–589 (2011).Crossref, Medline, CAS, Google Scholar
99 Sukumaran SK, Shimada H, Prasadarao NV. Entry and intracellular replication of Escherichia coli K1 in macrophages require expression of outer membrane protein A. Infect. Immun.71(10),5951–5961 (2003).Crossref, Medline, CAS, Google Scholar
100 Rolhion N, Barnich N, Bringer MA et al. Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent–invasive Escherichia coli invasion. Gut59(10),1355–1362 (2010).Crossref, Medline, CAS, Google Scholar
101 Sanjuan MA, Milasta S, Green DR. Toll-like receptor signaling in the lysosomal pathways. Immunol. Rev.227(1),203–220 (2009).Crossref, Medline, CAS, Google Scholar
102 Underhill DM, Goodridge HS. Information processing during phagocytosis. Nat. Rev. Immunol.12(7),492–502 (2012).Crossref, Medline, CAS, Google Scholar
103 Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature469(7330),323–335 (2011).Crossref, Medline, CAS, Google Scholar
104 Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol. Biol. Cell19(5),2092–2100 (2008).Crossref, Medline, CAS, Google Scholar
105 Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science313(5792),1438–1441 (2006).Crossref, Medline, CAS, Google Scholar
106 Lapaquette P, Bringer MA, Darfeuille-Michaud A. Defects in autophagy favour adherent–invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response. Cell. Microbiol.14(6),791–807 (2012).▪▪ Authors demonstrate that inhibition of ATG16L1, IRGM or NOD2 expression resulted in increased intramacrophagic replication of AIEC and increased secretion of IL-6 and TNF-α. This suggested that stimulating autophagy in CD patients could be a therapeutic strategy to control intracellular AIEC replication and slow down the inflammatory response.Crossref, Medline, CAS, Google Scholar
107 Fujita K, Srinivasula SM. TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS). Autophagy7(5),552–554 (2011).Crossref, Medline, CAS, Google Scholar
108 Chargui A, Cesaro A, Mimouna S et al. Subversion of autophagy in adherent invasive Escherichia coli-infected neutrophils induces inflammation and cell death. PLoS ONE7(12),e51727 (2012).Crossref, Medline, CAS, Google Scholar
109 Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-γ: an overview of signals, mechanisms and functions. J. Leukoc. Biol.75(2),163–189 (2004).Crossref, Medline, CAS, Google Scholar
110 Chang YP, Tsai CC, Huang WC et al. Autophagy facilitates IFN-γ-induced Jak2–STAT1 activation and cellular inflammation. J. Biol. Chem.285(37),28715–28722 (2010).Crossref, Medline, CAS, Google Scholar
111 Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu. Rev. Immunol.28,573–621 (2010).Crossref, Medline, CAS, Google Scholar
112 Huws SA, Morley RJ, Jones MV, Brown MR, Smith AW. Interactions of some common pathogenic bacteria with Acanthamoeba polyphaga. FEMS Microbiol. Lett.282(2),258–265 (2008).Crossref, Medline, CAS, Google Scholar
113 Greub G, Raoult D. Microorganisms resistant to free-living amoebae. Clin. Microbiol. Rev.17(2),413–433 (2004).Crossref, Medline, Google Scholar
114 Adiba S, Nizak C, Van Baalen M, Denamur E, Depaulis F. From grazing resistance to pathogenesis: the coincidental evolution of virulence factors. PLoS ONE5(8),e11882 (2010).Crossref, Medline, Google Scholar
115 Drouet M, Vignal C, Singer E et al. AIEC colonization and pathogenicity: influence of previous antibiotic treatment and preexisting inflammation. Inflamm. Bowel Dis.18(10),1923–1931 (2012).Crossref, Medline, Google Scholar
116 Carvalho FA, Koren O, Goodrich JK et al. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe12(2),139–152 (2012).Crossref, Medline, CAS, Google Scholar

Vol. 8, No. 10

Metrics

Downloaded 391 times

History

Published online 24 September 2013

Published in print October 2013

Information

Keywords

Acknowledgements

The authors would like to thank everyone who has contributed to the ongoing research into adherent–invasive Escherichia coli in the Clarke laboratory.

Financial & competing interests disclosure

Research in the Clarke laboratory is funded by the Irish Health Research Board and through the Alimentary Pharmabiotic Centre. The Alimentary Pharmabiotic Centre is a research center supported by Science Foundation Ireland (grant no. 07/CE/B1368). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download