Intimin

Intimin C-type lectin domain
nmr representative structure of intimin-190 (int190) from enteropathogenic e. coli
Identifiers
Symbol	Intimin_C
Pfam	PF07979
Pfam clan	CL0056
InterPro	IPR013117
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.^[1]

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.^[1] 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.^[2]

The structure of the C-terminal domain has been solved and shown to have a C-lectin type of structure.^[3] It is the C-terminal domain that mediates attachment to Tir.

It is a 94 kDa outer membrane protein encoded by eaeA gene in the locus of enterocyte effacement (LEE), a 35-Kb pathogenicity island.^[4] 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.^[5] 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:

1. Immune colostrum from mothers in EPEC endemic areas
2. The serum of EPEC/EHEC infected children and EPEC infected volunteers
3. Secretions of Citrobacter rodentium infected mice.

References

1. Stevens JM, Galyov EE, Stevens MP (February 2006). "Actin-dependent movement of bacterial pathogens". Nature Reviews. Microbiology. 4 (2): 91–101. doi:10.1038/nrmicro1320. PMID 16415925. S2CID 30946244.
2. Jerse AE, Yu J, Tall BD, Kaper JB (October 1990). "A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells". Proceedings of the National Academy of Sciences of the United States of America. 87 (20): 7839–43. doi:10.1073/pnas.87.20.7839. PMC 54845. PMID 2172966.
3. Batchelor M, Prasannan S, Daniell S, Reece S, Connerton I, Bloomberg G, Dougan G, Frankel G, Matthews S (June 2000). "Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli". The EMBO Journal. 19 (11): 2452–64. doi:10.1093/emboj/19.11.2452. PMC 212744. PMID 10835344.
4. McDaniel TK, Kaper JB (January 1997). "A cloned pathogenicity island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K-12" (PDF). Molecular Microbiology. 23 (2): 399–407. doi:10.1046/j.1365-2958.1997.2311591.x. PMID 9044273. S2CID 1403067.
5. Donnenberg MS, Tacket CO, James SP, Losonsky G, Nataro JP, Wasserman SS, Kaper JB, Levine MM (September 1993). "Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection". The Journal of Clinical Investigation. 92 (3): 1412–7. doi:10.1172/JCI116717. PMC 288285. PMID 8376594.

Further reading

• Ahmed S, Byrd W, Kumar S, Boedeker EC (March 2013). "A directed intimin insertion mutant of a rabbit enteropathogenic Escherichia coli (REPEC) is attenuated, immunogenic and elicits serogroup specific protection". Veterinary Immunology and Immunopathology. 152 (1–2): 146–55. doi:10.1016/j.vetimm.2012.09.035. PMID 23084628.

This article incorporates text from the public domain Pfam and InterPro: IPR013117