Grant: Operating Grant

Bacteria frequently exchange genetic material (DNA) with other bacterial species. By doing so they are able to rapidly evolve in response to their ever-changing environment. For example, bacterial genes responsible for antibiotic resistance are often obtained by genetic exchange; a major factor that accounts for the rapid spread of drug resistant bacteria in hospitals and communities. Bacterial genes involved in disease (virulence genes) are also typically transferred between bacterial species and this also has played a major role in the emergence of new pathogens. Genetic exchange can harm the bacterial cell, however, if the new genes they acquire are incompatible with the genes they already have. My laboratory has found that E. coli and Salmonella have a protein, called H-NS, that can distinguish self genes from those genes acquired from other bacteria and subsequently turn the foreign genes off. By shutting these genes off the bacteria can acquire foreign genes without compromising their own fitness by doing so. Over a longer period of time the bacteria can develop ways of turning the foreign genes on under the right conditions. Our lab and others have now determined that H-NS regulates the vast majority of virulence genes in bacteria that cause dysentery, plague, cholera and salmonellosis. In close collaboration with Dr. Jun Liu (U. Toronto) we also found a molecule that shuts down foreign DNA in Mycobacterium tuberculosis, the cause of tuberculosis, suggesting that shutting down foreign genes is a strategy commonly employed by many bacterial pathogens. Our future studies will determine exactly how H-NS and related proteins shut down newly acquired bacterial virulence genes and, subsequently, how such genes are turned on under the right conditions. By understanding these processes we hope to develop new therapeutic strategies for the control of bacterial infections.