Quorum sensing regulation of phenazine production heightens Pseudomonas aeruginosa resistance to ciprofloxacin

In this study, we grew Pseudomonas aeruginosa in the presence of sub-lethal concentrations of ciprofloxacin, resulting in a large increase in ciprofloxacin minimal inhibitory concentration. We discovered that quorum sensing mediated-phenazine biosynthesis was significantly enhanced in the resistant isolates, where the quinolone circuit, rather than acyl-homoserine lactone circuits, was the predominant contributor to this phenomenon. We found that production of pyocyanin changed carbon flux, and show that the effect can be partially inhibited by the addition of pyruvate to cultures. This study illustrates the role of quorum sensing-mediated phenotypic resistance and suggests a strategy for its prevention.