Specific Therapeutic Schemes of Omeprazole Affect the Orientation of
            <i>Helicobacter pylori</i>

Azevedo-Vethacke, Marina; Garten, Désirée; Groll, Claudia; Schreiber, S.

doi:10.1128/aac.00158-09

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…Pulsed omeprazole dosing in gerbils has also been shown to alter the orientation of H . pylori within the mucus layer relative to the gastric epithelium, which could promote bacterial clearance by driving the bacteria closer to the lumen or perhaps improving the efficiency of antibiotics [35]. Our results support these previous findings that reducing gastric acidity through proton pump inhibitor treatment changes bacterial density and distribution in the gastric glands, extending their range within this niche.…”

Section: Discussionsupporting

confidence: 89%

Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach

et al. 2017

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Helicobacter pylori’s ability to respond to environmental cues in the stomach is integral to its survival. By directly visualizing H. pylori swimming behavior when encountering a microscopic gradient consisting of the repellent acid and attractant urea, we found that H. pylori is able to simultaneously detect both signals, and its response depends on the magnitudes of the individual signals. By testing for the bacteria’s response to a pure acid gradient, we discovered that the chemoreceptors TlpA and TlpD are each independent acid sensors. They enable H. pylori to respond to and escape from increases in hydrogen ion concentration near 100 nanomolar. TlpD also mediates attraction to basic pH, a response dampened by another chemoreceptor TlpB. H. pylori mutants lacking both TlpA and TlpD (ΔtlpAD) are unable to sense acid and are defective in establishing colonization in the murine stomach. However, blocking acid production in the stomach with omeprazole rescues ΔtlpAD’s colonization defect. We used 3D confocal microscopy to determine how acid blockade affects the distribution of H. pylori in the stomach. We found that stomach acid controls not only the overall bacterial density, but also the microscopic distribution of bacteria that colonize the epithelium deep in the gastric glands. In omeprazole treated animals, bacterial abundance is increased in the antral glands, and gland colonization range is extended to the corpus. Our findings indicate that H. pylori has evolved at least two independent receptors capable of detecting acid gradients, allowing not only survival in the stomach, but also controlling the interaction of the bacteria with the epithelium.

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Section: Discussionsupporting

confidence: 89%

Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach

et al. 2017

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“…H. pylori furthermore are spatially oriented within the mucus layer based on pH gradients [7] . Disruption of these gradients, by equalizing luminal and surface pH, causes H. pylori to lose their direction of motion, and spread over the entire mucus layer [37] . Specifically, H. pylori are repelled by acidic regions in vitro , and this behavior is eliminated by deletion of one of the chemotaxis receptor genes, tlpB , as well as the general chemotaxis pathway [8] , [15] .…”

Section: Discussionmentioning

confidence: 99%

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

et al. 2014

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Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

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“…It has been reported that the efficacy of triple therapy treatment eradication of H. pylori, based on a per-protocol analysis, is comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. 43 It is well accepted that antibiotic resistance is a leading cause of eradication treatment failure, so tailored treatment based on antibiotic susceptibility testing might be more effective in the achievement of a high eradication rate when high resistances rates to Mtz or Cla are present in PU strains. Also, another cause that would affect the efficacy of eradication treatment is the increased free and long-term use of PPIs in Argentina to manage acid-related diseases usually associated with the alimentary habits of the population (e.g., intake of 70 kg of red meat per capita/year), which require digestive juices high in hydrochloric acid.…”

Section: Discussionmentioning

confidence: 99%