Bacteria detect neutrophils via a system that responds to hypochlorous acid and flow

Abstract Neutrophils respond to the presence of bacteria by producing oxidative molecules that are lethal to bacteria, including hypochlorous acid (HOCl). However, the extent to which bacteria detect activated neutrophils or the HOCl that neutrophils produce, has not been understood. Here we report that the opportunistic bacterial pathogen Pseudomonas aeruginosa upregulates expression of its fro operon in response to stimulated neutrophils. This operon was previously shown to be activated by shear rate of fluid flow in the environment. We show that fro is specifically upregulated by HOCl, while other oxidative factors that neutrophils produce including H2O2, do not upregulate fro. The fro-dependent response to HOCl upregulates the expression of multiple methionine sulfoxide reductases, which relieve oxidative stress that would otherwise inhibit growth. Our findings suggest a model in which the detection of shear rate or HOCl activates the fro operon, which serves as an early and sensitive host-detection system for P. aeruginosa that improves its own survival against neutrophil-mediated host defenses. In support of this model, we found that the fro operon is activated in an infection model where flow and neutrophils are present. This response could promote the bacterium’s pathogenicity, colonization of tissue, and persistence in infections.