Quorum Sensing and Host-Pathogen Communication in Salmonella Typhi

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Typhoid fever remains a major global health problem and is caused by the foodborne bacterium Salmonella Typhi. We are trying to understand how these bacteria communicate with each other to cause disease. Furthermore, we wish to investigate how Salmonella can eavesdrop on host cell communication for its benefit. Once Salmonella reach a critical population size, these communication systems enable them to co-ordinately regulate their biological activities and fitness. This allows the bacterial invaders to survive the hostile environment of the human host and invade in critically significant combat numbers to cause Typhoid fever. The bacterial and host cells communicate using chemical languages. We are trying to determine the chemical identity of the bacterial words used. This knowledge may provide insights into the nature of the cross-talk between Salmonella and the host. Once bacteria sense these chemical words they produce a synchronised response, ultimately altering their life-style and weaponry to successfully survive and replicate in the human host. We wish to identify the bacterial listening machinery and elucidate the mechanisms by which they respond and orchestrate these activities. Using state-of-the-art technologies we will determine which Salmonella genes and proteins are regulated by the bacterial and host-produced chemical words, and then determine how important these are for the process of infection. The knowledge gained from this research will allow us to develop new vaccines and anti-infective drugs to control disease.