A Novel Regulator of P. aeruginosa Virulence Genes

Junior Investigator and Project Leader

Deborah A. Hogan, Ph.D.
Associate Professor, Microbiology and Immunology
Geisel School of Medicine at Dartmouth
www.dartmouth.edu/~hoganlab

Research in the laboratory is focused on the characterization of novel virulence determinants in bacterial and fungal opportunistic pathogens. COBRE funded studies focus on a novel virulence factor regulator in the bacterium Pseudomonas aeruginosa. P. aeruginosa is an important pathogen of the lung and is associated with ventilator-associated pneumonia, chronic obstructive pulmonary disease, and chronic infections associated with cystic fibrosis (CF). Recent studies have identified a regulator, GbdR, that controls the production of a phospholipase C (PlcH), an enzyme that is a secreted by P. aeruginosa in the lung where it degrades phospholipids in lung surfactant and host cell membranes. The data show that GbdR is required for the induction of PlcH in the mouse lung, and for the formation of antibiotic-resistant biofilms on airway epithelial cells and in lung surfactant. Analysis of the GbdR regulon indicates that GbdR, either directly or indirectly, controls the expression of over 184 genes. The hypothesis to be tested is that GbdR coordinately regulates phospholipase C production with other virulence-related attributes. The specific aims of the project are to test the hypothesis that a subset of the genes that are differentially expressed in choline and PC-containing media are controlled by GbdR and are involved in virulence-related processes (Aim 1) and to identify the GbdR binding site in the plcH promoter and in the promoters of other GbdR-controlled genes (Aim 2). In Aim 3, studies will test the hypothesis that GbdR-controlled genes other than plcH participate in biofilm formation and virulence using defined P. aeruginosa mutants. Knowledge of pathways that contribute to biofilm formation and virulence may provide insight into novel ways to prevent or treat P. aeruginosa in the lung.

Dr. Hogan has collaborative, ongoing studies with past and current COBRE investigators as well as COBRE investigators in Vermont.