Helicobacter pylori Senses Bleach as a Chemoattractant Using a Cytosolic Chemoreceptor

Abstract

SUMMARYThe gastric pathogen Helicobacter pylori requires a non-canonical cytosolic chemoreceptor transducer-like protein D (TlpD) for efficient colonization of the mammalian stomach. Here we reconstituted a complete chemotransduction signaling complex in vitro with 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 that H. pylori is 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 from Salmonella enterica and Escherichia coli showed a similar reactivity toward bleach. We propose that this family of proteins enables host-associated bacteria to sense sites of tissue inflammation, a strategy that H. pylori uses to aid in colonizing and persisting in inflamed gastric tissue.

SpoT-Mediated NapA Upregulation Promotes Oxidative Stress-Induced Helicobacter pylori Biofilm Formation and Confers Multidrug Resistance

“…Some oxidative stress-regulatory genes, such as oxyR and rpoS ( 19 ), can also regulate the formation of bacterial biofilms. The genes that regulate the oxidative stress response in H. pylori include the cytoplasmic chemoreceptor (TlpD) ( 38 , 39 ), iron uptake regulation ( fur ) ( 30 ), posttranscriptional regulation ( csrA ) ( 40 ), and stress regulation ( spoT ) genes ( 41 ).…”

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenicEscherichia coliexquisitely resistant to reactive chlorine species

“…Many UPEC isolates express poly-GlcNAc during biofilm formation and host colonization making the polysaccharide a significant contributor to UPEC's virulence in vivo (45,87,88). The same Zn 2+ -binding domain and equivalent HOCl-sensing mechanism has been reported in chemoreceptors such as Helicobacter pylori TlpD, which facilitates chemoattraction to HOCl sources for H. pylori and potentially explains the persistence of this pathogen in inflamed tissue (89).…”

A new class of protein sensor links spirochete pleomorphism, persistence, and chemotaxis

“…Two of these domains, CZB and PAS domains, are established sensor domains. CZB domains are known to act as hypochlorous acid (HOCl) sensors in a wide variety of proteins from diverse bacteria, and can regulate protein activities in an HOCl-dependent manner 46,56 . PAS domains present in eukaryotes and prokaryotes and bind various ligands and/or proteins to modulate functionally diverse sensory pathways 57 .…”