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Discovery of sRNA-mediated gene regulation in Salmonella

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Salmonella enterica serovar Typhimurium is an adaptable and robust micro-organism that thrives in a variety of environmental niches, including the GI tract of humans, farm animals, birds and reptiles, and inside mammalian cells. To succeed as a pathogen, Salmonella relies upon a combination of regulatory proteins and two component systems to adapt the bacteria to every stage of infection. It has now become clear that small RNA molecules (sRNAs) mediate a relatively new type of gene regulation, and control the virulence of Listeria, Staphylococcus, Streptococcus and Vibrio. If we are to understand the aspects of Salmonella gene expression that are critical for survival, adaptation and disease, the sRNA biology of this important model pathogen must be defined.

We used a combination of chromatin immunoprecipitation and deep sequencing to identify the sRNAs of S. Typhimurium that are associated with Hfq (Sittka et al., 2008 PLoS Genetics 4: e1000163), and more than 130 sRNAs have now been experimentally verified in Salmonella. I will describe the role played by small regulatory RNA (sRNA) molecules in the rapid targeting and removal of mRNAs from the bacterial cell. The role of sRNA-mediated control of bacterial stress responses in transcriptional networks will be discussed.

We are currently identifying and auditing the sRNAs of S. Typhimurium expressed under multiple environmental conditions, including the infection process. Our comprehensive deep sequencing-based RNomic analysis has already identified hundreds of new Salmonella sRNAs. We have experimental evidence for 9 novel Salmonella-specific sRNAs that are expressed in a variety of environments. These include conditions that induce expression of Salmonella pathogenicity islands SPI1 and SPI2 , and within murine macrophages.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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