Role of EspB in experimental human enteropathogenic Escherichia coli infection

Enteropathogenic Escherichia coli (EPEC), a leading cause of diarrhea among infants in developing countries, induces dramatic alterations in host cell architecture that depend on a type III secretion system. EspB, one of the proteins secreted and translocated to the host cytoplasm via this system, i s required for numerous alterations in host cell structure and function. To determine the role of EspB in virulence, we conducted a randomized, double -blind trial comparing the ability of wild-type EPEC and an isogenic Delta espB mutant strain to cause diarrhea in adult volunteers. Diarrhea develope d in 9 of 10 volunteers who ingested the wild-type strain but in only 1 of 10 volunteers who ingested the Delta espB mutant strain. Marked destruction of the microvillous brush border adjacent to adherent organisms was observ ed in a jejunal biopsy from a volunteer who ingested the wild-type strain b ut not from two volunteers who ingested the Delta espB mutant strain. Humor al and cell-mediated immune responses to EPEC antigens were stronger among recipients of the wild-type strain. In addition, four of the volunteers who ingested the wild-type strain had lymphoproliferative responses to EspB. T hese results demonstrate that EspB is a critical virulence determinant of E PEC infections and suggest that EspB contributes to an immune response.