Exploiting gastric vulnerability

(Press-News.org) Helicobacter pylori infection promotes stomach ulcers and cancer. How H. pylori initially interacts with and irritates gastric tissue is not well understood. An article published on July 17th in PLOS Pathogens now describes that H. pylori rapidly identifies and colonizes sites of minor injuries in the stomach, almost immediately interferes with healing at those injury sites, and so promotes sustained gastric damage.

Smoking, alcohol, excessive salt intake, and non-steroidal anti-inflammatory drugs cause damage to the tissue lining the stomach, and are associated with stomach ulcers. A team of scientists led by Marshall Montrose, from the University of Cincinnati, USA, asked whether H. pylori can sense and respond to such damage and so contribute to disease development.

The researchers induced small stomach lesions in anesthetized mice and observed that H. pylori bacteria can rapidly detect the injury site and navigate toward it. Within minutes, accumulation of bacteria interferes with repair of the tissue damage—and these results are the earliest indication showing H. pylori causing disease.

To examine how the bacteria accomplish this, the researchers also studied mice with larger stomach lesions (ulcers) that were subsequently infected with H. pylori. They found that H. pylori preferentially colonizes stomach tissue at injured ulcer sites, and there impairs healing of the damaged tissue. Selective colonization requires both bacterial motility and chemotaxis (the ability to change direction of movement in response to environmental cues), and higher levels of bacterial accumulation cause slower healing. However, when extremely high levels of immotile or chemotaxis-deficient bacteria are added to damaged tissue, they can also slow healing. As the researchers explain, "it's like a tag team race. Chemotactic machinery guides H. pylori into the damage site to colonize, and then other virulence factors take over to make sure the site stays just as tasty in the long term by slowing repair of any damage".

While the signals that attract H. pylori (but not benign stomach bacteria) toward injured tissue are not yet known, the researchers hope that their ability to rapidly measure H. pylori accumulation at the injured site now provides an experimental set-up to determine the factor(s) involved.

"The broader implications of our work", the researchers say, "are that even subclinical insults to the stomach that occur in daily life (damage from grinding of food, ingestion of alcohol, taking an aspirin) can potentially attract H. pylori and not only slow repair of any existing damage, but maybe also provide an initiation site that can start the pathogenic sequence of more severe stomach diseases caused by H. pylori".

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Contact:
Marshall Montrose
e-mail: mhm@uc.edu
phone: +1.513.558.5636

Authors and Affiliations:
Eitaro Aihara, University of Cincinnati, USA
Chet Closson, University of Cincinnati, USA
Andrea L. Matthis, University of Cincinnati, USA
Michael A. Schumacher, University of Cincinnati, USA
Amy C. Engevik, University of Cincinnati, USA
Yana Zavros, University of Cincinnati, USA
Karen M. Ottemann, University of California at Santa Cruz, USA
Marshall H. Montrose, University of Cincinnati, USA

Funding: This work was supported by National Institutes of Health Grants RO1 DK54940 (MHM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Aihara E, Closson C, Matthis AL, Schumacher MA, Engevik AC, et al. (2014) Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori. PLoS Pathog 10(7): e1004275. doi:10.1371/journal.ppat.1004275