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 pathogenPseudomonas aeruginosaupregulates expression of itsfrooperon in response to stimulated neutrophils. This operon was previously shown to be activated by shear rate of fluid flow in the environment. We show thatfrois specifically upregulated by HOCl, while other oxidative factors that neutrophils produce including H2O2, do not upregulatefro. Thefro-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 thefrooperon, which serves as an early and sensitive host-detection system forP. aeruginosathat improves its own survival against neutrophil-mediated host defenses. In support of this model, we found that thefrooperon 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.
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