Enterohemorrhagic E. coli (EHEC) O157:H7 is responsible for major outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) throughout the world. One of the major problems in the control and prevention of EHEC outbreaks is the fact that it has a very low infectious dose. EHEC colonizes the large intestine where it causes attaching and effacing (AE) lesions, which are believed to be the first step toward infection of the host, and also produces Shiga toxins (Stx), which are responsible for the major symptoms of HUS. The genes involved in the formation of these AE lesions are encoded within a chromosomal pathogenicity island named the Locus of Enterocyte Effacement (LEE). We recently reported that both the LEE and the genes encoding Stx are activated by a bacterial cell-to-cell signaling mechanism known as quorum sensing (QS). Bacteria secrete hormone-like compounds, called autoinducers, which interact with bacterial transcriptional regulators to drive gene expression. The QS mechanism employed in this activation is involved in bacterial inter-species communication, and we propose that activation of EHEC virulence genes by this system may occur in response to autoinducers produced by the normal intestinal flora. This could, in part explain the low infectious dose of EHEC. ? ? This grant application in response to RFA (AI-02-008) """"""""Impact of microbial interactions on infections diseases"""""""" intends to study EHEC virulence gene expression in response to signals produced by the normal intestinal flora. Given that this RFA (AI-02-008) is designed to investigate the impact of microbial interactions on infectious diseases, including the interactions between pathogens and the normal flora, we feel that this grant application is particularly well suited to the mission of the RFA.
In Specific Aim 1, we propose to study EHEC gene expression at the genome level using DNA microarrays to assess EHEC responses to signals produced by the normal intestinal flora.
In Specific Aim 2, we propose to monitor EHEC virulence gene expression in a mixed population in the presence of the intestinal flora. ? ?
Showing the most recent 10 out of 12 publications
