Identification of a gene within a pathogenicity island of enterotoxigenic Escherichia coli H10407 required for maximal secretion of the heat-labile enterotoxin

Studies of the pathogenesis of enterotoxigenic Escherichia coli (ETEC) have largely centered on extrachromosomal determinants of virulence, in particu lar the plasmid-encoded heat-labile (LT) and heat-stable enterotoxins and t he colonization factor antigens. ETEC causes illnesses that range from mild diarrhea to severe cholera-like disease. These differences in disease seve rity are not readily accounted for by our current understanding of ETEC pat hogenesis. Here,ve demonstrate that Tia, a putative adhesin of ETEC H10407, is encoded on a large chromosomal element of approximately 46 kb that shar es multiple features with previously described E. coli pathogenicity island s. Further analysis of the region downstream from tin revealed the presence of several candidate open reading frames (ORFs) in the same transcriptiona l orientation as tia. The putative proteins encoded by these ORFs bear mult iple motifs associated with bacterial secretion apparatuses. An in-frame de letion in one candidate gene identified here as leoA (labile enterotoxin ou tput) resulted in marked diminution of secretion of the LT enterotoxin and lack of fluid accumulation in a rabbit ileal loop model of infection. Altho ugh previous studies have suggested that E. coli lacks the capacity to secr ete LT, our studies show that maximal release of LT from the periplasm of H 10407 is dependent on one or more elements encoded on a pathogenicity islan d.