Grant: Project Grant

With the discovery and use of the first antibiotics during the 1930's, the mortality or morbidity associated with infectious diseases have considerably decreased. However, over the years the use, abuse and misuse of antibiotics have selected for "superbugs" resistant to a wide spectrum of, and in some cases all known antimicrobial drugs. Multidrug resistant bacteria cause untreatable and hard-to-treat infections associated with high mortality rates and increased healthcare costs. Because microorganisms are increasingly resistant to antibiotics, and the pipeline of discovery and development of new antibiotics is slowly drying out, the World is now facing the risk of returning to a pre-antibiotic era, when even the most common infection was potentially fatal. It is now recognized that the emergence and propagation of "superbugs" are largely fueled by exchanges of genetic material (DNA) between microorganisms. The most potent mechanism of transmission of DNA between two bacterial cells is called conjugation. During conjugation, a multidrug resistant donor cell injects parts of its genome into a sensitive recipient cell and converts it into a multidrug resistant "superbug". The goal of our research project is to characterize key elements of the "syringe" and "needle" used by the donor cell to promote the injection of its DNA into the recipient cell. Understanding the molecular aspects of the mechanism promoting the exchange of antibiotic resistance genes will provide us with new targets for the rational design of new drugs aimed at blocking gene transfers to curb antibiotic resistance transmission between microorganisms causing infectious diseases in human and animals.