Helicobacter pylori Senses Bleach as a Chemoattractant Using a Cytosolic Chemoreceptor

Abstract

SUMMARYThe gastric pathogenHelicobacter pylorirequires a non-canonical cytosolic chemoreceptor transducer-like protein D (TlpD) for efficient colonization of the mammalian stomach. Here we reconstituted a complete chemotransduction signaling complexin vitrowith TlpD and the chemotaxis proteins CheW and CheA, enabling quantitative assays for potential chemotaxis ligands. We found that TlpD is selectively sensitive at micromolar concentrations to bleach (hypochlorous acid, HOCl), a potent antimicrobial produced by neutrophil myeloperoxidase during inflammation. Counterintuitively, HOCl acts as a chemoattractant by reversibly oxidizing a conserved cysteine within a 3His/1Cys Zn-binding motif in TlpD that inactivates the chemotransduction signaling complex. We found thatH. pyloriis resistant to killing by millimolar concentrations of HOCl and responds to bleach in the micromolar range by increasing its smooth swimming behavior, leading to chemoattraction to HOCl sources. We found that related protein domains fromSalmonella entericaandEscherichia colishowed a similar reactivity toward bleach. We propose that this family of proteins enables host-associated bacteria to sense sites of tissue inflammation, a strategy thatH. pyloriuses to aid in colonizing and persisting in inflamed gastric tissue.