TRANSLOCATED INTIMIN RECEPTORS (TIR) OF SHIGA-TOXIGENIC ESCHERICHIA-COLI ISOLATES BELONGING TO SEROGROUPS O26, O111, AND O157 REACT WITH SERA FROM PATIENTS WITH HEMOLYTIC-UREMIC SYNDROME AND EXHIBIT MARKED SEQUENCE HETEROGENEITY

The capacity to form attaching and effacing (A/E) lesions on the surfa ces of enterocytes is an important virulence trait of several enteric pathogens, including enteropathogenic Escherichia coli (EPEC) and Shig a-toxigenic E. coli (STEC). Formation of such lesions depends upon an interaction between a bacterial outer membrane protein (intimin) and a bacterially encoded receptor protein (Tir) which is exported from the bacterium and translocated into the host cell membrane. Intimin, Tir, and several other proteins necessary for generation of A/E lesions ar e encoded on a chromosomal pathogenicity island termed the locus for e nterocyte effacement (LEE). Reports of sequence heterogeneity and anti genic variation in the region of intimin believed to be responsible fo r receptor binding raise the possibility that the receptor itself is a lso heterogeneous. We have examined this by cloning and sequencing tir genes from three different STEC strains belonging to serogroups O26, O111, and O157. The deduced amino acid sequences for the Tir homologue s from these strains varied markedly, exhibiting only 65.4, 80.2, and 56.7% identity, respectively, to that recently reported for EPEC Tir. STEC Tir is also highly immunogenic in humans. Western blots off. coli DH5 alpha expressing the various STEC tir genes cloned in pBluescript [but not E. coli DH5 alpha(pBluescript)] reacted strongly with conval escent sera from patients with hemolytic-uremic syndrome (HUS) caused by known LEE-positive STEC. Moreover, no reaction was seen when the va rious clone lysates were probed with serum from a patient with HUS cau sed by a LEE-negative STEC or with serum from a healthy individual. Co variation of exposed epitopes on both intimin and Tir may be a means w hereby STEC avoid host immune responses without compromising adhesin-r eceptor interaction.