Our theme of gene-environment interactions — includes environmental signals that elicit alterations in gene expression to respond to that signal; this article [see attached] qualifies for that theme. Helicobacter pylori is a bacterial pathogen that is able to colonize the human stomach to cause gastritis (inflammation of stomach), ulcers, and stomach cancer. Despite triggering a robust inflammatory response, and bursts of reactive oxygen species (ROS) from immune cells, H. pylori often is able to avoid eradication (by antibiotics) and therefore the bacteria can persist for many decades. Not only is H. pylori not eradicated by inflammation; in fact, the pathogen is known to move toward sites of injury and may capitalize on tissue damage — by using the patient’s iron extracted from blood hemoglobin.
H. pylori relies on chemotaxis [movement by a cell, or organism (e.g. bacteria or paramecium) — in a direction corresponding to a gradient of increasing, or decreasing, concentration of a particular substance (environmental signal)] to seek sites optimal for growth and colonization within the hostile environment of the (highly acidic) stomach. Bacterial chemotaxis involves a well-studied phospho-relay system — prevalent across eubacteria and archaeabacteria — and functions via an evolutionarily conserved mechanism.
Chemoreceptor proteins typically possess a periplasmic (gel-like matrix in the space between the bacterial inner cytoplasmic membrane and outer membrane) “ligand-sensing domain” [a ‘ligand’ is a molecule that binds to another (usually larger) molecule] that recognizes small molecules and transduces signals across the inner membrane. Chemoreceptors in H. pylori, and other bacteria, oligomerize (form chains) to form trimers of receptor dimers — to build repeating hexagonal arrays; this process serves to amplify ligand-induced signals as much as 50-fold (i.e. a single activated receptor can initiate the signal transduction cascade)..!!
Authors [see attached article] reconstituted a complete chemotransduction signaling complex ‘in vitro’ (i.e. in a test tube) with TlpD and chemotaxis (Che) proteins CheW and CheA — enabling quantitative assays for potential chemotaxis ligands. Authors found that TlpD is selectively sensitive at microMolar concentrations to bleach (hypochlorous acid, HOCl), a potent antimicrobial produced by myeloperoxidase (in neutrophil white blood cells) during inflammation. HOCl acts as a chemoattractant by reversibly oxidizing a conserved cysteine within a 3His/1Cys Zn-binding motif (in the TlpD molecule) that inactivates the chemotransduction-signaling complex.
Authors found that H. pylori is resistant to killing by milliMolar concentrations of HOCl — and responds to HOCl in the microMolar range by increasing its smooth-swimming behavior, resulting in chemoattraction to HOCl sources. Authors show related protein domains from Salmonella enterica and Escherichia coli possess similar reactivity toward HOCl. Authors propose that this family of proteins most likely enables host-associated bacteria to “sense” sites of tissue inflammation, which would be a strategy that H. pylori uses to aid in colonizing and persisting in inflammatory stomach tissue. 😊
PLoS Biol Aug 2019; 17: e3000395