Regulation and Role in Pathogenesis of Megaplasmid-encoded Virulence Factors of Shiga Toxin producing Escherichia coli

点击翻译按钮获取中文摘要

Shiga toxin producing Escherichia coli (STEC) cause serious gastrointestinal infections in humans, which can lead to potentially fatal systemic complications, such as the haemolytic uraemic syndrome (HUS). The pathology of STEC disease has long been considered to be directly attributable to the production of Shiga toxin (Stx). However, there is increasing evidence that STEC strains vary in their capacity to cause serious disease. Although the amount or subtype of Stx produced by a given strain clearly plays a role, putative accessory virulence factors encoded on chromosomal pathogenicity islands (PAI) or megaplasmids are also important. This project is part of a large on-going research program aimed at characterizing virulence factors of STEC and identifying targets for novel vaccines and drugs. It will focus on factors encoded by the STEC megaplasmids, particularly those from strains that lack the locus of enterocyte effacement (LEE). LEE-negative STEC megaplasmids are much larger than those from LEE-positive strains such as O157:H7 (160 vs 92 kb), and encode a number of unique proteins whose role in pathogenesis is unknown. The principal aim of project described here is to identify which of these megaplasmid genes are expressed under conditions that mimic those which occur in vivo. This will enable us to target individual genes for mutagenesis, such that their contribution to pathogenesis can be assessed in animal models.