Intimin

{{Infobox protein family | Symbol = Intimin_C | Name = Intimin C-type lectin domain | image = PDB 1e5u EBI.jpg | width = | caption = nmr representative structure of intimin-190 (int190) from enteropathogenic e. coli | Pfam = PF07979 | Pfam_clan = CL0056 | InterPro = IPR013117 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Intimin''' is a virulence factor (adhesin) of EPEC (''e.g.'' ''E. coli'' O127:H6) and EHEC (''e.g. E. coli'' O157:H7) ''E. coli'' strains. It is an attaching and effacing (A/E) protein, which with other virulence factors is necessary and responsible for enteropathogenic and enterohaemorrhagic diarrhoea.<ref name="pmid16415925">{{cite journal | vauthors = Stevens JM, Galyov EE, Stevens MP | title = Actin-dependent movement of bacterial pathogens | journal = Nature Reviews. Microbiology | volume = 4 | issue = 2 | pages = 91–101 | date = February 2006 | pmid = 16415925 | doi = 10.1038/nrmicro1320 | s2cid = 30946244 | doi-access = free | hdl = 2381/15179 | hdl-access = free }}</ref>

Intimin is expressed on the bacterial cell surface where it can bind to its receptor Tir (Translocated intimin receptor). Tir, and over 25 other bacterial proteins are secreted from attaching and effacing ''E. coli'' directly into the cytoplasm of intestinal epithelial cells by a Type three secretion system. Once within the cytoplasm of the host cell, Tir is inserted into the plasma membrane, allowing surface exposure and intimin binding.<ref name="pmid16415925" /> Tir-intimin interaction mediates tight binding of enteropathogenic and enterohaemorrhagic ''E.coli'' to the intestinal epithelia, resulting in the formation of effacing lesions on intestinal epithelia.<ref>{{cite journal | vauthors = Jerse AE, Yu J, Tall BD, Kaper JB | title = A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 20 | pages = 7839–43 | date = October 1990 | pmc = 54845 | doi=10.1073/pnas.87.20.7839 | pmid=2172966| doi-access = free }}</ref>

The structure of the C-terminal domain has been solved and shown to have a C-lectin type of structure.<ref name="pmid10835344">{{cite journal | vauthors = Batchelor M, Prasannan S, Daniell S, Reece S, Connerton I, Bloomberg G, Dougan G, Frankel G, Matthews S | title = Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli | journal = The EMBO Journal | volume = 19 | issue = 11 | pages = 2452–64 | date = June 2000 | pmid = 10835344 | pmc = 212744 | doi = 10.1093/emboj/19.11.2452 }}</ref> It is the C-terminal domain that mediates attachment to Tir.

It is a 94 kDa outer membrane protein encoded by ''eae''A gene in the locus of enterocyte effacement (LEE), a 35-Kb pathogenicity island.<ref name="pmid9044273">{{cite journal | vauthors = McDaniel TK, Kaper JB | title = A cloned pathogenicity island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K-12 | journal = Molecular Microbiology | volume = 23 | issue = 2 | pages = 399–407 | date = January 1997 | pmid = 9044273 | doi = 10.1046/j.1365-2958.1997.2311591.x | s2cid = 1403067 | url = http://thewatchers.us/EPA/13/1997-K-12-AE-island.pdf | archive-date = 2018-04-16 | access-date = 2018-04-16 | archive-url = https://web.archive.org/web/20180416073613/http://thewatchers.us/EPA/13/1997-K-12-AE-island.pdf | url-status = dead }}</ref> Mutations in the ''eaeA'' gene result in loss of ability to cause A/E lesions, and is required for full virulence in infected volunteers and animal models.<ref name="pmid8376594">{{cite journal | vauthors = Donnenberg MS, Tacket CO, James SP, Losonsky G, Nataro JP, Wasserman SS, Kaper JB, Levine MM | title = Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection | journal = The Journal of Clinical Investigation | volume = 92 | issue = 3 | pages = 1412–7 | date = September 1993 | pmid = 8376594 | pmc = 288285 | doi = 10.1172/JCI116717 }}</ref> The N-terminal domains of intimin from A/E lesion forming pathogens have high homology with each other and to invasin from ''Yersinia pseudotuberculosis'' and ''Yersinia enterocolitica'', whereas the C-terminal domains show less homology.

Antibodies to intimin are present in:

# Immune colostrum from mothers in EPEC endemic areas # The serum of EPEC/EHEC infected children and EPEC infected volunteers # Secretions of ''Citrobacter rodentium'' infected mice. {{clear}}

== References == {{reflist|32em}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Ahmed S, Byrd W, Kumar S, Boedeker EC | title = A directed intimin insertion mutant of a rabbit enteropathogenic Escherichia coli (REPEC) is attenuated, immunogenic and elicits serogroup specific protection | journal = Veterinary Immunology and Immunopathology | volume = 152 | issue = 1–2 | pages = 146–55 | date = March 2013 | pmid = 23084628 | doi = 10.1016/j.vetimm.2012.09.035 }} {{refend}}

Category:Membrane channels Category:Protein domains Category:Virulence factors