Abstract
Adherent-invasive Escherichia coli (AIEC) has recently attracted more attention because it is closely related to the pathogenicity of human inflammatory bowel disease (IBD). AIEC possesses a multitude of virulence factors. Considering these virulence factors belonging to various virulence groups, including adhesins, invasins, toxins, protectins, and siderophore-mediated iron acquisition, this review summarizes the current knowledge of how the major virulence factors assisting in AIEC survive in, adhere to, and invade host cells. A comprehensive understanding of the interaction of virulence factors with host cells will provide us a new therapeutic strategy for IBD prevention and treatment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agus A, Denizot J, Thevenot J, Martinez-Medina M, Massier S, Sauvanet P, Bernalier-Donadille A, Denis S, Hofman P, Bonnet R, Billard E, Barnich N (2016) Western diet induces a shift in microbiota composition enhancing susceptibility to adherent-invasive E. coli infection and intestinal inflammation. Sci Rep 6:19032. https://doi.org/10.1038/srep19032
Alvarez Dorta D, Sivignon A, Chalopin T, Dumych TI, Roos G, Bilyy RO, Deniaud D, Krammer EM, de Ruyck J, Lensink MF, Bouckaert J, Barnich N, Gouin SG (2016) The antiadhesive strategy in Crohn’s disease: orally active mannosides to decolonize pathogenic Escherichia coli from the gut. Chembiochem 17(10):936–952. https://doi.org/10.1002/cbic.201600018
Barnich N, Boudeau J, Clare L, Darfeuille-Michaud A (2003) Regulatory and functional co-operation of flagella and type 1 pili in adhesive and invasive abilities of AIEC strain LF82 isolated from a patient with Crohn’s disease. Mol Microbiol 48(3):781–794
Barnich N, Carvalho FA, Glasser AL, Darcha C, Jantscheff P, Allez M, Peeters H, Bommelaer G, Desreumaux P, Colombel JF, Darfeuille-Michaud A (2007) CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest 117(6):1566–1574. https://doi.org/10.1172/JCI30504
Barratt-Due A, Pischke SE, Nilsson PH, Espevik T, Mollnes TE (2017) Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets. J Leukoc Biol 101(1):193–204. https://doi.org/10.1189/jlb.3VMR0316-132R
Boudeau J, Barnich N, Darfeuille-Michaud A (2001) Type 1 pili-mediated adherence of Escherichia coli strain LF82 isolated from Crohn’s disease is involved in bacterial invasion of intestinal epithelial cells. Mol Microbiol 39(5):1272–1284
Cario E (2005) Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2. Gut 54(8):1182–1193. https://doi.org/10.1136/gut.2004.062794
Carvalho FA, Barnich N, Sivignon A, Darcha C, Chan CH, Stanners CP, Darfeuille-Michaud A (2009) Crohn’s disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM. J Exp Med 206(10):2179–2189. https://doi.org/10.1084/jem.20090741
Carvalho FA, Koren O, Goodrich JK, Johansson ME, Nalbantoglu I, Aitken JD, Su Y, Chassaing B, Walters WA, Gonzalez A, Clemente JC, Cullender TC, Barnich N, Darfeuille-Michaud A, Vijay-Kumar M, Knight R, Ley RE, Gewirtz AT (2012) Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12(2):139–152. https://doi.org/10.1016/j.chom.2012.07.004
Chakraborty A, Adhikari P, Shenoy S, Saralaya V (2016) Virulence factor profiles, phylogenetic background, and antimicrobial resistance pattern of lactose fermenting and nonlactose fermenting Escherichia coli from extraintestinal sources. Indian J Pathol Microbiol 59(2):180–184. https://doi.org/10.4103/0377-4929.182032
Chassaing B, Etienne-Mesmin L, Bonnet R, Darfeuille-Michaud A (2013) Bile salts induce long polar fimbriae expression favouring Crohn’s disease-associated adherent-invasive Escherichia coli interaction with Peyer's patches. Environ Microbiol 15(2):355–371. https://doi.org/10.1111/j.1462-2920.2012.02824.x
Chassaing B, Koren O, Carvalho FA, Ley RE, Gewirtz AT (2014) AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition. Gut 63(7):1069–1080. https://doi.org/10.1136/gutjnl-2013-304909
Chouikha I, Bree A, Moulin-Schouleur M, Gilot P, Germon P (2008) Differential expression of iutA and ibeA in the early stages of infection by extra-intestinal pathogenic E. coli. Microbes Infect 10(4):432–438. https://doi.org/10.1016/j.micinf.2008.01.002
Cieza RJ, Hu J, Ross BN, Sbrana E, Torres AG (2015) The IbeA invasin of adherent-invasive Escherichia coli mediates interaction with intestinal epithelia and macrophages. Infect Immun 83(5):1904–1918. https://doi.org/10.1128/IAI.03003-14
Coppens F, Iyyathurai J, Ruer S, Fioravanti A, Taganna J, Vereecke L, De Greve H, Remaut H (2015) Structural and adhesive properties of the long polar fimbriae protein LpfD from adherent-invasive Escherichia coli. Acta Crystallogr D Biol Crystallogr 71(Pt 8):1615–1626. https://doi.org/10.1107/S1399004715009803
Deng W, Puente JL, Gruenheid S, Li Y, Vallance BA, Vazquez A, Barba J, Ibarra JA, O'Donnell P, Metalnikov P, Ashman K, Lee S, Goode D, Pawson T, Finlay BB (2004) Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A 101(10):3597–3602. https://doi.org/10.1073/pnas.0400326101
Dogan B, Suzuki H, Herlekar D, Sartor RB, Campbell BJ, Roberts CL, Stewart K, Scherl EJ, Araz Y, Bitar PP, Lefebure T, Chandler B, Schukken YH, Stanhope MJ, Simpson KW (2014) Inflammation-associated adherent-invasive Escherichia coli are enriched in pathways for use of propanediol and iron and M-cell translocation. Inflamm Bowel Dis 20(11):1919–1932. https://doi.org/10.1097/MIB.0000000000000183
Dong X, Liu Z, Lan D, Niu J, Miao J, Yang G, Zhang F, Sun Y, Wang K, Miao Y (2017) Critical role of keratin 1 in maintaining epithelial barrier and correlation of its down-regulation with the progression of inflammatory bowel disease. Gene. https://doi.org/10.1016/j.gene.2017.01.015
Dreux N, Denizot J, Martinez-Medina M, Mellmann A, Billig M, Kisiela D, Chattopadhyay S, Sokurenko E, Neut C, Gower-Rousseau C, Colombel JF, Bonnet R, Darfeuille-Michaud A, Barnich N (2013) Point mutations in FimH adhesin of Crohn’s disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response. PLoS Pathog 9(1):e1003141. https://doi.org/10.1371/journal.ppat.1003141
Duan Q, Zhou M, Zhu X, Yang Y, Zhu J, Bao W, Wu S, Ruan X, Zhang W, Zhu G (2013) Flagella from F18+Escherichia coli play a role in adhesion to pig epithelial cell lines. Microb Pathog 55:32–38. https://doi.org/10.1016/j.micpath.2012.09.010
Eaves-Pyles T, Murthy K, Liaudet L, Virag L, Ross G, Soriano FG, Szabo C, Salzman AL (2001) Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction. J Immunol 166(2):1248–1260. https://doi.org/10.4049/jimmunol.166.2.1248
Fahlgren A, Baranov V, Frangsmyr L, Zoubir F, Hammarstrom ML, Hammarstrom S (2003) Interferon-gamma tempers the expression of carcinoembryonic antigen family molecules in human colon cells: a possible role in innate mucosal defence. Scand J Immunol 58(6):628–641. https://doi.org/10.1111/j.1365-3083.2003.01342.x
Gibold L, Garenaux E, Dalmasso G, Gallucci C, Cia D, Mottet-Auselo B, Fais T, Darfeuille-Michaud A, Nguyen HT, Barnich N, Bonnet R, Delmas J (2016) The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli. Cell Microbiol 18(5):617–631. https://doi.org/10.1111/cmi.12539
Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A (2001) Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect Immun 69(9):5529–5537. https://doi.org/10.1128/iai.69.9.5529-5537.2001
Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, Busse L, Zukowski MM, Wright SD (1994) Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 179(1):269–277. https://doi.org/10.1084/jem.179.1.269
Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832):1099–1103. https://doi.org/10.1038/35074106
He Y, Liu S, Kling DE, Leone S, Lawlor NT, Huang Y, Feinberg SB, Hill DR, Newburg DS (2016) The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut 65(1):33–46. https://doi.org/10.1136/gutjnl-2014-307544
Henderson IR, Navarro-Garcia F, Desvaux M, Fernandez RC, Ala'Aldeen D (2004) Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev 68(4):692–744. https://doi.org/10.1128/MMBR.68.4.692-744.2004
Huang S, Wan Z, Chen Y, Jong A, Kim KS (2001) Further characterization of Escherichia coli brain microvascular endothelial cell invasion gene ibeA by deletion, complementation, and protein expression. J Infect Dis 183(7):1071–1078. https://doi.org/10.1086/319290
Khan KJ, Ullman TA, Ford AC, Abreu MT, Abadir A, Marshall JK, Talley NJ, Moayyedi P (2011) Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 106(4):661–673. https://doi.org/10.1038/ajg.2011.72
Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM (2004) Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 113(9):1296–1306. https://doi.org/10.1172/jci200420295
Maciel JF, Matter LB, Trindade MM, Camillo G, Lovato M, de Avila Botton S, Castagna de Vargas A (2017) Virulence factors and antimicrobial susceptibility profile of extraintestinal Escherichia coli isolated from an avian colisepticemia outbreak. Microb Pathog 103:119–122. https://doi.org/10.1016/j.micpath.2016.12.020
Mirsepasi-Lauridsen HC, Du Z, Struve C, Charbon G, Karczewski J, Krogfelt KA, Petersen AM, Wells JM (2016) Secretion of alpha-hemolysin by Escherichia coli disrupts tight junctions in ulcerative colitis patients. Clin Transl Gastroenterol 7:e149. https://doi.org/10.1038/ctg.2016.3
Najjar M, Saleh D, Zelic M, Nogusa S, Shah S, Tai A, Finger JN, Polykratis A, Gough PJ, Bertin J, Whalen MJ, Pasparakis M, Balachandran S, Kelliher M, Poltorak A, Degterev A (2016) RIPK1 And RIPK3 kinases promote cell-death-independent inflammation by toll-like receptor 4. Immunity 45(1):46–59. https://doi.org/10.1016/j.immuni.2016.06.007
Oh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, Hakimpour P, Gill KP, Nakaya HI, Yarovinsky F, Sartor RB, Gewirtz AT, Pulendran B (2014) TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41(3):478–492. https://doi.org/10.1016/j.immuni.2014.08.009
Park BS, Song DH, Kim HM, Choi B-S, Lee H, Lee J-O (2009) The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex. Nature 458(7242):1191–1195. https://doi.org/10.1038/nature07830
Parreira VR, Gyles CL (2003) A novel pathogenicity island integrated adjacent to the thrW tRNA gene of avian pathogenic Escherichia coli encodes a vacuolating autotransporter toxin. Infect Immun 71(9):5087–5096. https://doi.org/10.1128/iai.71.9.5087-5096.2003
Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007) Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 76:295–329. https://doi.org/10.1146/annurev.biochem.76.010307.145803
Ramos HC, Rumbo M, Sirard JC (2004) Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends Microbiol 12(11):509–517. https://doi.org/10.1016/j.tim.2004.09.002
Rolhion N, Carvalho FA, Darfeuille-Michaud A (2007) OmpC and the sigma(E) regulatory pathway are involved in adhesion and invasion of the Crohn’s disease-associated Escherichia coli strain LF82. Mol Microbiol 63(6):1684–1700. https://doi.org/10.1111/j.1365-2958.2007.05638.x
Rooks MG, Veiga P, Reeves AZ, Lavoie S, Yasuda K, Asano Y, Yoshihara K, Michaud M, Wardwell-Scott L, Gallini CA, Glickman JN, Sudo N, Huttenhower C, Lesser CF, Garrett WS (2017) QseC inhibition as an antivirulence approach for colitis-associated bacteria. Proc Natl Acad Sci U S A 114(1):142–147. https://doi.org/10.1073/pnas.1612836114
Ryu JK, Kim SJ, Rah SH, Kang JI, Jung HE, Lee D, Lee HK, Lee JO, Park BS, Yoon TY, Kim HM (2017) Reconstruction of LPS transfer cascade reveals structural determinants within LBP, CD14, and TLR4-MD2 for efficient LPS recognition and transfer. Immunity 46(1):38–50. https://doi.org/10.1016/j.immuni.2016.11.007
Schaefer L (2014) Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289(51):35237–35245. https://doi.org/10.1074/jbc.R114.619304
Shaulov L, Gershberg J, Deng W, Finlay BB, Sal-Man N (2017) The ruler protein EscP of the enteropathogenic Escherichia coli type III secretion system is involved in calcium sensing and secretion hierarchy regulation by interacting with the gatekeeper protein SepL. MBio 8(1). https://doi.org/10.1128/mBio.01733-16
Sivignon A, Yan X, Alvarez Dorta D, Bonnet R, Bouckaert J, Fleury E, Bernard J, Gouin SG, Darfeuille-Michaud A, Barnich N (2015) Development of Heptylmannoside-based glycoconjugate antiadhesive compounds against adherent-invasive Escherichia coli bacteria associated with Crohn’s disease. MBio 6(6):e01298–e01215. https://doi.org/10.1128/mBio.01298-15
Szebeni B, Veres G, Dezsofi A, Rusai K, Vannay A, Mraz M, Majorova E, Arato A (2008) Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease. Clin Exp Immunol 151(1):34–41. https://doi.org/10.1111/j.1365-2249.2007.03531.x
Tan Y, Kagan JC (2014) A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide. Mol Cell 54(2):212–223. https://doi.org/10.1016/j.molcel.2014.03.012
Wang B, Han Y, Li Y, Li Y, Wang X (2015) Immuno-stimulatory activity of Escherichia coli mutants producing Kdo2-monophosphoryl-lipid A or Kdo2-pentaacyl-monophosphoryl-lipid A. PLoS One 10(12):e0144714. https://doi.org/10.1371/journal.pone.0144714
Wehkamp J, Frick JS (2016) Microbiome and chronic inflammatory bowel diseases. J Mol Med (Berl) 95(1):21–28. https://doi.org/10.1007/s00109-016-1495-z
Zhou M, Yang Y, Chen P, Hu H, Hardwidge PR, Zhu G (2015) More than a locomotive organelle: flagella in Escherichia coli. Appl Microbiol Biotechnol 99(21):8883–8890. https://doi.org/10.1007/s00253-015-6946-x
Acknowledgements
The authors specially thank Dr. Philip Hardwidge for the great help on the critical manuscript review.
Funding
This study was supported by Grant No. 2016YFD0500905 from the National Key Research and Development Program of China, grants from the Chinese National Science Foundation Grant (Nos. 31672579, 30571374, 30771603, 31072136, 31270171), a project founded by the Priority Academic Program of Development Jiangsu High Education Institution, No. 2015M581875 from China Postdoctoral Science Foundation, No. 1501117B from Jiangsu Planned Projects for Postdoctoral Research Funds.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yang, Y., Liao, Y., Ma, Y. et al. The role of major virulence factors of AIEC involved in inflammatory bowl disease—a mini-review. Appl Microbiol Biotechnol 101, 7781–7787 (2017). https://doi.org/10.1007/s00253-017-8507-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-017-8507-y