Role of EspF in host cell death induced by enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli (EPEC) causes diarrhoea in children in de veloping countries. Many EPEC genes involved in virulence are contained wit hin the locus of enterocyte effacement (LEE), a large pathogenicity island. One of the genes at the far righthand end of the LEE encodes EspF, an EPEC secreted protein of unknown function. EspF, like the other Esps, is a subs trate for secretion by the type III secretory system. Previous studies foun d that an espF mutant behaved as wild type in assays of adherence, invasion , actin condensation and tyrosine phosphorylation. As EPEC can kill host ce lls, we tested esp gene mutants for host cell killing ability. The espF mut ant was deficient in host cell killing despite having normal adherence. The addition of purified EspF to tissue culture medium did not cause any damag e to host cells, but expression of espF in COS or HeLa cells caused cell de ath. The mode of cell death in cells transfected with espF appeared to be p ure apoptosis. EspF appears to be an effector of host cell death in epithel ial cells; its proline-rich structure suggests that it may act by binding t o SH3 domains or EVH1 domains of host cell signalling proteins.