Grant: Doctoral: Vanier Canada Graduate Scholarships

Cystic fibrosis (CF) is the most common fatal genetic disorder in Canada. Patients with CF have extremely thick mucus in their lungs, which creates an environment that inevitably allows for growth of harmful bacteria, such as Pseudomonas aeruginosa. Once P. aeruginosa infects the lungs of a CF patient, the infection can never be cured in spite of aggressive treatment with antibiotics because P. aeruginosa forms a biofilm, which is a surface-attached bacterial community that protects the bacteria from antibiotics and the patient's immune system. Previous work has shown that the ndvB gene is expressed by P. aeruginosa growing in a biofilm, and that ndvB contributes to antibiotic resistance and persistence of P. aeruginosa biofilms. Therefore, preventing ndvB from being expressed in biofilms should make P. aeruginosa infections more susceptible to clearance by the immune system and by antibiotics. However, the mechanisms that cause ndvB to be expressed in biofilms are not understood. The aims of this project are to understand the molecular basis for ndvB expression in biofilms as well as to discover new molecules that specifically prevent ndvB from being expressed. The knowledge that will be gained from this project will provide the research community with important information on the factors that control ndvB expression in biofilms, and these factors may one day be used as novel drug targets. Perhaps more importantly, this research project will also identify molecules that can prevent ndvB from being expressed. In the future, these molecules could be developed into new medications that would decrease antibiotic resistance in P. aeruginosa biofilms, thereby increasing the effectiveness of the antibiotics that CF patients must take to treat their lung infections.