Gene regulation plays a critical role in the virulence of pathogenic bacteria. Our long-term goal is to understand how transcription factors (TFs) regulate virulence processes in the pathogenic species, Enterotoxigenic Escherichia coli (ETEC). ETEC is the leading bacterial cause of diarrhea in the developing world and causes >300,000 deaths annually, mainly in children. Many virulence genes have been identified in ETEC but relatively little is known about regulation of these genes. We have recently identified a TF, RoaA, encoded on one of the ETEC virulence plasmids, that is required for efficient adhesion to gut epithelial cells. We hypothesize that RoaA is a key regulator of ETEC virulence. The goal of this proposal is to comprehensively identify the regulatory targets of RoaA with nucleotide resolution. We will use complementary genomic approaches, ChIP-seq and RNA-seq, to identify direct and indirect regulatory targets. We will determine which of the target genes are required for ETEC virulence. We will then use genetic and biochemical analyses to identify the precise DNA sites for RoaA at the promoters of these genes. The proposed work will provide important insight into the regulation of ETEC virulence genes, and will form the foundation of future studies of ETEC virulence.

Public Health Relevance

NARRATIVE Enterotoxigenic Escherichia coli (ETEC) kills more than 300,000 people annually. We have identified an ETEC regulatory protein that is required for efficient attachment to human gut epithelial cells. We will identify the regulatory targets of this protein.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI094245-01
Application #
8091726
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Baqar, Shahida
Project Start
2011-03-01
Project End
2013-02-28
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
1
Fiscal Year
2011
Total Cost
$70,012
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
153695478
City
Menands
State
NY
Country
United States
Zip Code
12204