Our long-term research goal is to study the molecular mechanisms of how enteropathogenic E. coli (EPEC) causes disease. We currently have three projects underway. The first area of study concerns the regulation of EPEC virulence factors by a novel protein called Ler. Funding for this has included a three-year, NIH AREA grant (2R15AI47802-03).
|Model for Action of Ler at LEE promoters. Figure from Haack et al. (2003) Infection and Immunity 71: 384-392. Arrow notes direction of transcription.|
A second project involves delineating the regulatory network controlling the initial stages of EPEC infection. We have determined that the plasmid-encoded regulator, PerC, in addition to ler, controls a number of genes involved in manipulation of the host innate immune system. Thus we are interested in how PerC confers a predicted selective advantage to the bacterium at the site of infection- the small intestine, and the molecular mechanism by which this small regulatory protein controls gene expression. This project is funded by the M.J. Murdock Charitable Trust and an NIH Exploratory/Developmental Research Award (1R21AI115193-01, 2015-2017).
Virulence gene regulation on the E. coli attachment factor plasmid (pEAF) of EPEC. Figure from Mellies et al. (2007) Infection and Immunity 75: 4199-4210. PerC controls expression of the LEE1 operon, encoding components of a type III secretion system necessary for virulence.
A third project is directed at understanding the effects of zinc on E. coli pathogenesis. Children with diarrhea in developing countries have less severe disease if they are given zinc tablets. This is not due to zinc deficiencies in their diets, but rather to unknown effects on the bacteria. This project involves understanding the molecular mechanisms of how zinc down-regulates virulence gene expression in enteropathogenic E. coli and is supported by a collaborative NIH grant with Dr. John Crane at the University of Buffalo (5R01AI081528-02).
The effects of zinc stress on the EPEC envelope imaged by transmission electron microscopy. Figure from Mellies et al. (2012) BMC Microbiology 12: 123. Arrow points to outer membrane blebs in (D). (A,D) Bars 1.0 μm; (B-C,D-F) Bars 0.1 μm.
Lab Folks 2017/18
Research Associates: Amy Platenkamp, Morgan Vague
Thesis Students: Eliotte Garling, Katie McPherson, Jethary Rader, and Trevor Soucy
Independent Study: Colin Hawkinson