Post-transcriptional regulation of virulence in Campylobacter jejuni

Project: Research project

Project Details

Description

ABSTRACT
Campylobacter jejuni is a leading bacterial cause of gastroenteritis in the United States, and is responsible
for sporadic disease as well as food-borne and water-borne outbreaks. It is also a Category B Bioterrorism
Agent. There are at least 2 million cases of C. jejuni gastroenteritis each year in the U.S.;an incidence equal
or greater to that of Salmonella and Shigella combined. A subset of C. jejuni infections lead to the
development of Guillain-Barr[unreadable] Syndrome, an acute motor paralysis apparently resulting from an autoimmune
response directed at C. jejuni surface antigens mimicking gangliosides. Despite the high prevalence of
Campylobacter disease and more than 20 years of study, the mechanisms by which C. jejuni causes disease
remain obscure. Several C. jejuni virulence factors have been identified, yet the mechanisms by which they
are regulated remain largely unknown.
Recently we have begun characterization of the C. jejuni ortholog of the post-transcriptional regulator CsrA.
In other bacteria, CsrA mediates the regulation of numerous important virulence phenotypes, including carbon
metabolism, motility, quorum sensing, biofilm production and others. CsrA activity is controlled by inducible
small regulatory RNAs (sRNAs) that bind competitively to CsrA. We have constructed a C. jejuni mutant
lacking csrA, and have shown that the csrA mutant exhibits pleiotropic virulence-related phenotypes including
decreased motility, epithelial cell adherence, biofilm formation, and resistance to oxidative stress (including
ambient air, hydrogen peroxide, and superoxide). Conversely, the csrA mutant shows increased invasion of
human epithelial cells. This underscores the importance of the CsrA regulon in C. jejuni pathogenesis.
Overall hypothesis: Campylobacter jejuni CsrA plays an important role in the pathogenesis of C. jejuni via
the post-transcriptional regulation of virulence properties.
We propose a detailed study of CsrA-mediated post-transcriptional gene regulation in C. jejuni, focusing on the
mechanism by which CsrA controls the expression of virulence properties. We will use genetic, proteomic and
biochemical approaches to achieve the goals outlined in these three specific aims: Aim 1) Continue
characterizing the CsrA regulon and cis-acting factors required for CsrA regulation of these proteins, Aim 2)
Identify and characterize the sRNA component that antagonizes CsrA activity, and Aim 3) Identify
environmental conditions and regulatory proteins that control expression of csrA.
StatusFinished
Effective start/end date7/19/107/18/12

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)