Grant: Operating Grant

Just as humans inherit certain traits from generation to generation, the same is true of bacteria that inherit genetic information from their ancestors. This genetic information specifies not only what type of bacteria it will become, but also how it interacts with it's surroundings, whether it will be pathogenic or not, and whether it is resistant to certain antibiotics for example. We have identified new mechanisms of pathogen evolution whereby bacteria alter the expression of certain genes in response to the host. By altering their regulatory DNA, bacteria can turn genes on or off at certain times or produce more of a certain gene product when it is needed most, allowing them to rapidly respond to their environment and exploit the immediate surroundings, such as in a human or animal host. We found that when bacteria can mutate their regulatory DNA, they are better able to infect animal hosts, however we don't yet know the full extent to which bacteria use this strategy for their virulence or to adapt during human and animal infection. Our work examines how bacterial pathogens sense their host surroundings and the mechanisms that link these host sensors to adaptive gene expression involved in virulence, evasion of our immune system, and ultimately, disease. Using new technologies in genomics and microbial chemical biology, we are creating an unprecedented opportunity for insight into the interface of human and microbial biology by generating new knowledge about infectious disease mechanisms. This knowledge base creates opportunities for innovative drug target discovery with tangible impact into public health.