A Quorum Sensing Regulated Small Volatile Molecule Reduces Acute Virulence and Promotes Chronic Infection Phenotypes
Figure 5
2-AA promotes phenotypes associated with pathogenic bacteria at chronic infection sites.
(A) 2-AA promotes increased accumulation of lasR mutations in PA14 and mutS cells in a concentration-dependent manner. Data are averages of two independent experiments, performed in triplicate. Significance of difference in number of lasR mutants was calculated using Student's t-test, assuming equal variance. Asterisks represent significant differences relative to the untreated control group. For both PA14 and mutS mutant cells, lasR mutant accumulation was significantly increased with 100 µg/ml and 200 µg/ml 2-AA (p's = 0.02 and 0.0001 for PA14, and p's = 0.05 and 0.01 for mutS, respectively). (B) 2-AA promotes prolonged stationary phase growth. Untreated PA14 cells began to lyse by 40 h, whereas PA14 cells treated with 2-AA at all tested concentrations did not. (C) 2-AA promotes persistent infection in flies. Bacterial CFUs per fly were assessed at 7 d post-P. aeruginosa feeding (6–9 flies per time point). Significant differences in CFUs after 7 d were seen for pqsA (pink) versus PA14 (black) or pqsB::C (green); Student's t-test p values are indicated in the figure. The data presented were combined from two independent experiments. (D) A model for 2-AA function. As the volatile (squiggly grey lines) 2-AA accumulates overtime in a microenvironment (i.e. biofilms, wounds or CF lungs) it creates a heterogeneous population of cells that consists of WT and physiologically and genetically different cells. The unaltered WT cells undergo lysis. On the other hand, the subpopulation of cells with silenced MvfR can continue to accumulate mutations that are beneficial for adaption to chronic infection.