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Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach.

ABSTRACT: 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 (?tlpAD) 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 ?tlpAD'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.

SUBMITTER: Huang JY

PROVIDER: S-EPMC5245789 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach.

Huang Julie Y JY Goers Sweeney Emily E Guillemin Karen K Amieva Manuel R MR

PLoS pathogens 20170119 1

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 Tlp ...[more]

PMID: 28103315

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Project description:BackgroundNineteen non-antibacterials were examined to show that their consumption for treatment of other diseases may inhibit Helicobacter pylori. Four antibiotics were used for comparison.Materials and methodsAgar dilution method was used to examine the susceptibility of 20 H. pylori isolates to 4 antibiotics; metronidazole (MTZ), clarithromycin (CLR), amoxicillin (AMX), tetracycline (TET) and 19 non-antibacterials; proton pump inhibitors (PPIs), H2-blockers, bismuth subsalicylate (BSS), antifungals, statins, acetaminophen (ACE), aspirin (ASA), B-vitamins (B-Vits; Vit B1, Vit B6 and Vit Bcomplex) and vitamin C (Vit C). Blood agar plates were prepared with different concentrations of drugs and spot-inoculated with bacterial suspensions. Plates were incubated at 37 °C under microaerobic conditions and examined after 3-5 days. The isolate #20 that was mucoid and resistant to 19 drugs, including MTZ and SMV was tested against combined MTZ (8 μg/mL) and SMV (100 μg/mL). Results were analyzed statistically.ResultsMinimum inhibitory concentrations (MICs, μg/mL) of drugs and the frequency of susceptible H. pylori were determined as MTZ (8, 80%), CLR (2, 90%), AMX (1, 100%), TET (0.5, 70%), PPIs (8-128, 80%), H2-blockers (2000-8000, 75-80%), BSS (15, 85%), antifungals (64-256, 30-80%), statins (100-250, 35-90%), ACE (40, 75%), ASA (800, 75%), B-Vits (5000-20000, 80-100%) and Vit C (2048, 85%). Susceptibility of H. pylori isolates to 16 out of 19 non-antimicrobials (75-100%) was almost similar to those of antibiotics (70-100%) (P-value >0.05). The highest susceptibility rate (100%) belonged to Vit B1, Vit B6 and AMX. Out of 20 H. pylori isolates, 17 (85%) were susceptible to ≥13 non-antimicrobials and 3 (15%) were susceptible to < 13 (P-value <0.05). Mucoid H. pylori showed susceptibility to combination of MTZ and SMV.ConclusionsMost of non-antibacterials inhibited H. pylori isolates, similar to antibiotics but their MICs exceeded those of antibiotics and their plasma concentrations. At low plasma concentration, non-antimicrobials may act as weak antibacterials, antibiotic adjuvants and immunostimulators.

Dataset Information

Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach.

Publications

Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach.

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