<i>Pseudomonas Virulence</i> <i>Factor</i> Produces Autoinducer (<i>S</i>)-Valdiazen

<i>Pseudomonas virulence</i> <i>factor</i> (<i>pvf</i>) produces an autoinducing small-molecule signal that regulates bacterial cell-to-cell communication and virulence. While genes like <i>pvf</i> have been linked to the production of small molecules containing a diazeniumdiolate group, the specific chemical signal produced by <i>pvf</i> had not been identified. In this study, we reveal that (<i>S</i>)-valdiazen is the autoinducer produced by <i>pvf</i> in <i>Pseudomonas entomophila</i>, a model for pathogen-host interactions. The (<i>S</i>)-configuration is crucial for the signaling activity of valdiazen at physiological concentrations. We also define the (<i>S</i>)-stereochemistry of leudiazen, a similar signal produced by the plant pathogen <i>Pseudomonas syringae</i>. Using <i>pvf</i> genes needed for (<i>S</i>)-valdiazen signaling and production in <i>P. entomophila</i>, we bioinformatically identified 5383 bacterial organisms that may produce diazeniumdiolate signals. Signaling activity of valdiazen can be quenched by potassium permanganate, which oxidizes the diazeniumdiolate moiety. Identification of (<i>S</i>)-diazeniumdiolates from two bacterial species suggests stereospecific biosynthesis and transduction of these signals. Our findings set the stage for discovering diazeniumdiolate signals from other bacteria.