: Enteropathogenic E. coli (EPEC) is an important cause of diarrhea of infants living in developing countries. EPEC is the prototype organism of a group of pathogenic bacteria that cause intestinal attaching and effacing (AE) lesions. All genes necessary for the AE phenotype are encoded within a 35.6 kb pathogenicity island (PAl) termed the locus of enterocyte effacement, or LEE. A virulence plasmid-encoded regulator, PerABC, was previously described in EPEC. We have shown that the expression of a novel LEE-encoded regulator, Ler, is increased by PerABC. As part of a regulatory cascade, Ler then activates transcription of four polycistronic operons of the LEE, which includes at least 24 of the 41 predicted LEE ORFs. Ler also controls the expression of genes located outside the LEE. Thus, Ler is a novel global regulator of EPEC virulence genes. Our long-term research goal is to understand how appropriate expression of EPEC virulence factors occurs within the human intestine. During this period of support, we will characterize the cis-acting sequences necessary for Ler-mediated activation of the LEE2 and tir promoters, determine whether Ler alone is sufficient for activation of these prototypical promoters, and determine whether Ler affects RNA polymerase binding at LEE2 and tir. Through these genetic and biochemical studies we will obtain a greater understanding of the molecular pathogenesis of EPEC. EPEC and E. coli serotype O157:H7, a member of the enterohemorrhagic E. coli (EHEC) category of E. coil, are related pathogens. In the U.S., EHEC is of particular concern in food safety and public health because this organism has caused many outbreaks of bloody diarrhea due to contaminated meat products, produce and water. Through the study of EPEC virulence gene regulation we will also gain insight into the molecular pathogenesis of EPEC.
| Mellies, Jay L; Benison, Gregory; McNitt, William et al. (2011) Ler of pathogenic Escherichia coli forms toroidal protein-DNA complexes. Microbiology 157:1123-33 |
| Mellies, Jay L; Lawrence-Pine, Emily R (2010) Interkingdom signaling between pathogenic bacteria and Caenorhabditis elegans. Trends Microbiol 18:448-54 |
| Mellies, Jay L; Larabee, Fredrick J; Zarr, Melissa A et al. (2008) Ler interdomain linker is essential for anti-silencing activity in enteropathogenic Escherichia coli. Microbiology 154:3624-38 |
| Mellies, Jay L; Barron, Alex M S; Carmona, Anna M (2007) Enteropathogenic and enterohemorrhagic Escherichia coli virulence gene regulation. Infect Immun 75:4199-210 |
| Mellies, Jay L; Haack, Kenneth R; Galligan, Derek C (2007) SOS regulation of the type III secretion system of enteropathogenic Escherichia coli. J Bacteriol 189:2863-72 |
| Haack, Kenneth R; Robinson, Christopher L; Miller, Kristie J et al. (2003) Interaction of Ler at the LEE5 (tir) operon of enteropathogenic Escherichia coli. Infect Immun 71:384-92 |
