Pseudomonas aeruginosa is an opportunistic pathogen associated with a large number of infections that impact millions worldwide. One important virulence factor for this organism is the production of redox-active metabolites called phenazines. Phenazines are a double-edged sword. While on the one hand, they play important physiological roles in the survival of their producers;on the other, they can cause oxidative damage to both the host and members of the associated microbial community. A large hole in our understanding of phenazines is how P. aeruginosa defends itself against their toxic effects. This proposal will focus on understanding how P. aeruginosa modulates the concentration and redox activity of phenazines to maximize fitness. I hypothesize that P. aeruginosa utilizes a two-fold strategy to deal with these metabolites when their negative effects outweigh the positive: (i) sequestration and shielding from the environment and (ii) active degradation. Insights gained from this work will help us to understand the in vivo physiology of this important human pathogen, and will influence how we think about and respond to P. aeruginosa during infection.

Public Health Relevance

Phenazine production is essential for the opportunistic human pathogen Pseudomonas aeruginosa to persist during infection. However, these molecules are double-edged swords in that they help the producers maintain cellular redox homeostasis but generate toxic reactive oxygen species as a byproduct of this activity. This proposal aims to understand how P. aeruginosa defends itself against the toxic effects of its own phenazine metabolites.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI112248-01
Application #
8716319
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Taylor, Christopher E,
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
None
Type
Schools of Arts and Sciences
DUNS #
City
Pasadena
State
CA
Country
United States
Zip Code
91125