RNA-binding proteins in bacterial virulence and host-pathogen interactions

PROJECT SUMMARY The ability of bacteria to rapidly sense and respond to changes in the environment is fundamental to colonization. Post-transcriptional regulation is emerging as an important strategy that promotes efficient and precise control of bacterial virulence, and thus plays a central role in pathogenesis. Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a bacterial pathogen that colonizes the human colon and causes severe hemorrhagic colitis and hemolytic uremic syndrome (HUS), which can be fatal. EHEC is able to efficiently acquire nutrients and coordinate expression of traits that promote intestinal colonization, suggesting that EHEC has evolved mechanisms to spatiotemporally control virulence gene expression to occur within appropriate host niches. RNA binding proteins play important roles in bacterial gene expression by modulating transcription termination, RNA stability, and translation; however, the targets and molecular mechanisms of most RNA binding proteins and the corresponding impact on bacterial virulence and host interactions are poorly resolved. The proposed work will elucidate the regulatory mechanisms of RNA binding proteins and importance to fitness within the intestine, as well as examine how these RNA binding proteins are activated within transcriptional networks and in response to host cues.