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.
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.
| Costa, Kyle C; Moskatel, Leon S; Meirelles, Lucas A et al. (2018) PhdA Catalyzes the First Step of Phenazine-1-Carboxylic Acid Degradation in Mycobacterium fortuitum. J Bacteriol 200: |
| Costa, Kyle C; Glasser, Nathaniel R; Conway, Stuart J et al. (2017) Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms. Science 355:170-173 |
| Costa, Kyle C; Bergkessel, Megan; Saunders, Scott et al. (2015) Enzymatic Degradation of Phenazines Can Generate Energy and Protect Sensitive Organisms from Toxicity. MBio 6:e01520-15 |
