Grant: Operating Grant

Understanding how the major hospital pathogen Pseudomonas aeruginosa adapts to host conditions, and development of new treatment approaches. Pseudomonas aeruginosa (PA) is a bacterium that continues to be a major cause of hospital-acquired infections (180,000/year in North America). PA is naturally resistant to certain antibiotics, and it is able to further adapt to the presence of antibiotics, and other situations it encounters in infections, to become even more resistant (termed adaptive resistance). Therefore, PA infections are very difficult to treat. We were involved in sequencing the first PA genome in 2000, providing a genetic blueprint for this organism. This blueprint has shown us that PA is tremendously complex and has revealed clues as to the basis for this organism being a feared pathogen. The genetic complexity of PA is mirrored by its ability to adopt specific 'lifestyles' under particular circumstances (e.g., association with the lung surface or antibiotic exposure). Many of these lifestyle changes are relevant to human infections because they increase the ability of PA to infect and persist in patients, and facilitate the development of adaptive antibiotic resistance. Our studies will continue to investigate the underlying basis for these lifestyles, and how certain genes impact on the ability of this bacterium to cause infections and antibiotic resistance. Our work will contribute to understanding lifestyles that are relevant to human infections, and will provide an improved comprehension of a very important and deadly pathogen. These studies will continue to yield information that will impact future treatments. In this regard we have identified small proteins, termed peptides, capable of specifically inhibiting PA undergoing these lifestyle changes, for example swarming, which is one of several ways bacteria can move. We will thus investigate whether these peptides assist in resolving extremely antibiotic resistant infections.