The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenicand enterohemorrhagic Escherichia coli

Regulation of virulence gene expression in enteropathogenic Escherichia col i (EPEC) and enterohemorrhagic E, coli (EHEC) is incompletely understood. I n EPEC, the plasmid-encoded regulator Per is required for maximal expressio n of proteins encoded on the locus of enterocyte effacement (LEE), and a LE E-encoded regulator (Ler) is part of the Per-mediated regulatory cascade up regulating the LEE2, LEE3, and LEE4 promoters. We now report that Ler is es sential for the expression of multiple LEE-located genes in both EPEC and E HEC, including those encoding the type III secretion pathway, the secreted Esp proteins, Tir, and intimin. Ler is therefore central to the process of attaching and effacing (AE) lesion formation. Ler also regulates the expres sion of LEE-located genes not required for AE-lesion formation, including r orf2, orf10, rorf10, orf19, and espF, indicating that Ler regulates additio nal virulence properties. In addition, Ler regulates the expression of prot eins encoded outside the LEE that are not essential for AE lesion formation , including TagA in EHEC and EspC in EPEC. Delta ler mutants of both EPEC a nd EHEC show altered adherence to epithelial cells and express novel fimbri ae, Ler is therefore a global regulator of virulence gene expression in EPE C and EHEC.