Species specificity and tissue tropism of EPEC and related pathogens

Abstract

Pathogens that cause attaching and effacing (A/E) lesions in infected host cells, including enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC, respectively), Hafnia alvei and Citrobacter rodantium, exhibit species specificity and tissue tropism[1xDonnenberg, M.S., Kaper, J.B., and Finlay, B.B. Trends Microbiol. 1997; 5: 109–114Abstract | Full Text PDF | PubMed | Scopus (201)See all References[1]. In many cases, these involve specific attachment. In EPEC and related pathogens, intimin is the adhesin that has been implicated in mediating colonization and tissue tropism. Dr Kaper's recent, thoughtful article in Trends Microbiol. on the virulence of EPEC (Ref. [2xKaper, J.B. Trends Microbiol. 1998; 6: 169–172Abstract | Full Text | Full Text PDF | PubMed | Scopus (57)See all References[2]) describes new aspects of EPEC infection; among these is the realization that EPEC and EHEC translocate the intimin receptor (Tir/EspE) into the host cell[3xKenny, B. et al. Cell. 1997; 91: 511–520Abstract | Full Text | Full Text PDF | PubMedSee all References, 4xDeibel, C. et al. Mol. Microbiol. 1998; 28: 463–474Crossref | PubMed | Scopus (142)See all References]. Thus, intimin does not seem to recognize a tissue-specific component but instead recognizes a translocated receptor. Indeed, in their response to Kaper's article, Finlay et al.[5xFinlay, B.B. et al. Trends Microbiol. 1998; 6: 172–173Abstract | Full Text | Full Text PDFSee all References[5]ponder what mechanism is used by EPEC for tissue tropism.Recently, we demonstrated that the EPEC type III secretion system is activated upon contact with epithelial cells[6xWolff, C. et al. Mol. Microbiol. 1998; 28: 143–155Crossref | PubMed | Scopus (170)See all References[6]. This is not surprising, as similar results have been obtained with type III secretion systems of Shigella, Salmonella and Yersinia[7xLee, C.A. Trends Microbiol. 1997; 5: 148–156Abstract | Full Text PDF | PubMed | Scopus (170)See all References[7]. An attractive hypothesis is that the elusive recognition process that triggers type III secretion systems might be a tissue-specific event. This event would dictate where Tir and EspE are translocated and thus dictate the site of colonization. An additional layer of specificity might reside in initial attachment, as contact activation of the type III secretion system and translocation of EspB and Tir are dependent upon attachment to the host cell[6xWolff, C. et al. Mol. Microbiol. 1998; 28: 143–155Crossref | PubMed | Scopus (170)See all References[6]. Currently, intimin is the only EPEC factor known to function as an adhesin in vivo[8xHicks, S. et al. Infect. Immun. 1998; 66: 1570–1578PubMedSee all References[8]. It is possible that the presumably weak and Tir-independent attachment activity of intimin[9xFrankel, G. et al. J. Biol. Chem. 1996; 271: 20359–20364Crossref | PubMed | Scopus (150)See all References[9], or some other adhesin, plays a role in jump-starting an efficient translocation process. Once a small amount of Tir is translocated, EPEC establishes an intimate contact and enters into a phase of enhanced translocation[6xWolff, C. et al. Mol. Microbiol. 1998; 28: 143–155Crossref | PubMed | Scopus (170)See all References[6]. At this stage, Tir-independent attachment activity is no longer needed.A third layer of specificity might reside in the transcriptional regulation of expression of the type III secretion system in response to environmental cues. For example, human-specific EPEC secretes Esps at 37°C but not at 42°C. In contrast, 42°C, which is the body temperature of rabbits, is the optimal temperature for Esp secretion by rabbit-specific EPEC (RDEC-1)[10xAbe, A. et al. Infect. Immun. 1997; 65: 3547–3555PubMedSee all References[10].It remains to be seen whether this hypothesis for EPEC species specificity and tissue tropism will stand up to testing. A critical point is to define, at the molecular level, the events that mediate the contact activation of the type III secretion system of EPEC.