Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

The Burkholderia cepacia complex (Bcc) is a group of multiple antibiotic resistant bacteria that infect cystic fibrosis patients. Once established, the infection is virtually impossible to eradicate. For this reason, new and more effective antibiotics are urgently needed. Antibiotics work by interfering with functions important for bacterial life (essential functions). Thus, research on new antibiotics involves not only discovering new compounds with antibiotic activity but also finding the essential functions that these molecules target. To find novel antibiotics we screened a collection of more than 30,000 small molecules and found compounds that inhibit the growth of B. cenocepacia K56-2, a clinical isolate of Bcc. Using molecular genetics tools, we are building a large collection of bacterial mutants in which each clone contains an essential function that can be controlled. We will expose these mutants to the growth inhibitors and by observing the different responses of the clones we will identify the essential functions targeted by the small molecules. Our research will provide novel antibacterial molecules against Bcc and the understanding of how such molecules kill the bacteria. This knowledge will be very important for further developments of the novel antibacterial molecules into more effective ways to treat Bcc infections.