Grant: Operating Grant

Small regulatory RNAs (sRNAs) are relatively newly identified players in the genetic regulation of bacterial pathogens. Some of them have been shown to be essential during infection and are proposed to be novel, as yet unexploited, targets for antibiotherapy. Many sRNAs have been previously identified in Legionella pneumophila, but the functions of most of them are currently unknown. L. pneumophila is the causative agent of Legionnaires' disease, an acute pulmonary infection in humans. It is able to infect and grow inside human lung macrophages, immune cells that normally fight off invading bacteria. As such, L. pneumophila is a model to study intracellular pathogens. For this project, we are proposing to explore the roles of sRNAs during infection of host cells by L. pneumophila, such as the regulation of virulence functions. In addition, we are proposing to study a possible direct role of sRNAs during intracellular growth, since our preliminary data indicates that sRNAs could be transferred from the bacterium to the host cell to modify the function of the latter. Accordingly, sRNAs could act independently as virulence factors. We have already identified several candidate sRNAs that could potentially be involved during infection. We will use an array of cutting edge genetic and molecular techniques to investigate their functions. This project has the potential to find new interactions between bacterial pathogens and host cells, and to find new targets for antibiotherapy.