Grant: Project Grant

With the discovery and use of the first antibiotics during the 1930s, the mortality and morbidity associated with infectious diseases have considerably decreased. However, over the years, the usage, abuse and misuse of antibiotics have selected "superbugs" resistant to a broad 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 bacteria are increasingly resistant to antibiotics, and the pipeline of discovery and development of new antibiotics is slowly drying out, the World is now edging a return to a pre-antibiotic era, when even the most common infection was potentially fatal. The frequent exchange of genetic material (DNA) between bacteria facilitates the emergence and propagation of "superbugs". 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". Our research project will characterize two natural mechanisms that limit the transmission of DNA between cells: surface and entry exclusion. Surface exclusion inhibits cell-cell contact, whereas entry exclusion prevents DNA transfer between pairs of mating cells. We will explore whether we can manipulate these mechanisms to reduce the efficiency of DNA transfer. Furthermore, we will investigate how the transferred DNA, recognized as non-self by the recipient cell, can bypass defence systems to persist in the new host. Understanding the molecular aspects of these mechanisms will provide new targets for the rational design of new drugs that curb antibiotic resistance transmission between microorganisms causing infectious diseases in humans and animals.