Grant: Project Grant

Antibiotics are the most successful medicine in human history, saving lives and underpinning the success of many medical procedures including surgeries, transplantations and chemotherapy. Their continuing success is threatened by the inexorable rise of multidrug resistance (MDR) coupled to the dearth of new antimicrobial discovery. Our research to date has helped to shed light on an insidious and important cause of MDR termed "adaptive resistance" that depends on the growth circumstances (lifestyle) of the bacterium. We have been studying this with respect to Pseudomonas aeruginosa that continues to be a major cause of life-threatening hospital-acquired infections (180,000/year in North America). P. aeruginosa is intrinsically 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. Therefore, P. aeruginosa infections are very difficult to treat. 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 (multidrug) antibiotic resistance and infections (virulence). This work will contribute to understanding lifestyles (growth on surfaces as biofilms, motility adaptations, in vivo growth, antibiotics) that are relevant to human infections, using genomic methods with very detailed outputs, and will continue to yield information that will impact on future treatments. In this regard we have identified small proteins, termed peptides, capable of specifically inhibiting P. aeruginosa undergoing these lifestyle changes, for example swarming motility and biofilm formation, which are two lifestyles this bacterium can adopt. It is our intention to enter the clinic with such a peptide treatment within the requested period of grant funding.