Guest Speaker Seminar - Dr. Dao Nguyen - Thursday, Nov. 18, 2010

Dr. Dao Nguyen

Assistant Professor
Department of Medicine
McGill University

"The role of starvation responses in Pseudomonas aeruginosa antibiotic tolerance"

Abstract

The successful treatment of bacterial infections requires bacteria to be eradicated. When host defenses are compromised, bacterial killing by antibiotics is critical. Bacteria can develop phenotypic multi-drug tolerance without harboring any inheritable mechanism of resistance, and the mechanisms of tolerance remain largely unknown. Bacteria become tolerant under several growth conditions, most notably when depleted for nutrients. We are investigating whether starvation confers tolerance by inducing a specific response, the stringent response, mediated by (p)ppGpp. Nutrient starvation and induction of the stringent response may also be the common mechanism underlying the marked tolerance observed in both stationary phase and biofilm growth. We studied the opportunistic pathogen Pseudomonas aeruginosa to investigate whether disruption of the stringent response impaired antibiotic tolerance in-vitro and in-vivo, and how (p)ppGpp mediated tolerance. The stringent response, a non-essential highly conserved bacterial stress response, may be an attractive and novel therapeutic target to enhance the efficacy of antibiotic treatments against tolerant infections, such as Pseudomonas aeruginosa biofilm infections.