At least five proteins are secreted extracellularly by enteropathogenic Esc
herichia coli (EPEC), a leading cause of infant diarrhea in developing coun
tries. However only one, EspC, is known to be secreted independently of the
type III secretion apparatus encoded by genes located within the 35.6-kb l
ocus of enterocyte effacement pathogenicity island. EspC is a member of the
autotransporter family of proteins, and the secreted portion of the molecu
le is 110 kDa. Here we determine that the espC gene is located within a sec
ond EPEC pathogenicity island at 60 min on the chromosome of E. coli. We al
so show that EspC is an enterotoxin, indicated by rises in short-circuit cu
rrent and potential difference in rat jejunal tissue mounted in Ussing cham
bers. In addition, preincubation with antiserum against the homologous Pet
enterotoxin of enteroaggregative E. coli eliminated EspC enterotoxin activi
ty. Like the EAF plasmid, the espC pathogenicity island was found only in a
subset of EPEC, suggesting that EspC may play a role as an accessory virul
ence factor in some but not all EPEC strains.