Grant: Discovery Grants Program - Individual

The long-term goal of our research program is to discern how multi-drug resistant bacteria found in the soil environment adapt to and persist in the niches they colonize. These bacteria are important sources of molecules for the elimination of environmental pollutants (bioremediation) as well as for controlling infections of crops (biocontrol). However, these bacteria also cause infections in immunosuppressed patients, which detract us from taking full advantage of their beneficial properties. The ability of these bacteria to adapt to humans as well as to survive in the environment interacting with multiple organisms depends on bacterial global regulatory networks. These networks control the expression of key bacterial molecules that are critical for niche adaptation. Our model system for our studies is Burkholderia cenocepacia. This bacterium is a significant cause of opportunistic infections in Canadian patients with cystic fibrosis. At the same time, these bacteria can metabolize a wide range of toxic chemical compounds and produce antifungal and antibacterial substances. Some strains are capable of living in plant cells establishing a harmonious lifestyle with the host (endosymbionts), while others parasite free-living amoebae and human phagocytes, causing their destruction. We believe that the ability of these bacteria to adapt to survive in association with a broad range of hosts, together with their extraordinary resistance to most antimicrobials, may be critical to their ability to cause devastating opportunistic infections in humans. Very little is known about the molecular basis for this broad adaptability, but we will focus our research program on characterizing a specific regulatory molecule as well as the network of genes it controls. This is a novel global regulator that controls biofilm formation, bacterial adherence to cells, and the expression of a secretion system that mediates the secretion of bacterial toxins into the host cells. We speculate that inhibiting this network will help discover novel strategies to curtail infections by opportunistic bacteria, while improving the use of their beneficial properties.