Grant: Project Grant

To cause infection, free-living bacteria must sense the presence of a host and activate virulence mechanisms. Bacterial virulence relies on the ability to utilize host-derived nutrients as well as capacity to evade and suppress host immunity. While many of the physiological changes associated with transitions to pathogenesis have been extensively studied, how bacteria sense the presence of a host and make a decision to transition from free living to pathogenic are largely unknown. Using a combination of forward and reverse genetics, we have identified genes in the ESKAPE pathogen Pseudomonas aeruginosa required for sensing and persisting in association with a mammalian host and causing disease. We have found that inducible outer membrane modifications, regulated by the ColR/S two component system, promote host association. We also discovered that bacterial sensing of exogenous polyamines regulates biofilm formation and promotes pathogenesis. This work combines in vitro studies with validation in a mouse chronic infection (abscess) model to understand how ColR/S and polyamine signaling facilitate bacterial lifestyle transitions. This work will shed light on how microbes transition from free-living to pathogenic and elucidate potential targets for antibiotic development.