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Helicobacter pylori infection and antibiotic resistance — from biology to clinical implications

Abstract

Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance — single drug resistance, multidrug resistance and heteroresistance — seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.

Key points

  • Antibiotic resistance in Helicobacter pylori is a global threat to human health.

  • Attributes driving this resistance include mainly mutations encoded chromosomally but also physiological changes such as impaired regulation of drug uptake and/or efflux, and biofilm and coccoid formation.

  • H. pylori frequently displays three different profiles of resistance including single drug resistance, multidrug resistance and heteroresistance, probably with nested fundamental mechanisms and clinical implications.

  • In individual patients, mechanisms of resistance deployed by H. pylori cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes.

  • At the population scale, increasing antibiotic resistance has globally led to a substantial decrease in H. pylori treatment efficacy and probably an increased risk of complications such as peptic ulcers and gastric cancer.

  • To fight this resistance, efforts needed include development of efficient vaccines, setting new treatment strategies, improving diagnostic tools for optimizing clinical decisions, and a better understanding of driving mechanisms.

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Fig. 1: Biological attributes of resistance in Helicobacter pylori species.
Fig. 2: Scanning electron microscopy images of a biofilm-forming Helicobacter pylori strain.
Fig. 3: Development of heteroresistance in Helicobacter pylori species.

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Acknowledgements

The work of Y.Y. was funded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT; 26640114, 15H02657, 16H05191, 16H06279, 18KK0266, 19H03473) and the Japan Society for the Promotion of Science (JSPS) Institutional Program for Core-to-Core Program, and the B. Africa-Asia Science Platform.

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Both authors researched data for the article, made substantial contributions to discussion of the content and reviewed/edited the manuscript before submission. E.T.-K wrote the article. Both authors read and agreed to the published version of the article.

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Correspondence to Yoshio Yamaoka.

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Nature Reviews Gastroenterology & Hepatology thanks A. Link, H. Suzuki, A. Zullo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Tshibangu-Kabamba, E., Yamaoka, Y. Helicobacter pylori infection and antibiotic resistance — from biology to clinical implications. Nat Rev Gastroenterol Hepatol (2021). https://doi.org/10.1038/s41575-021-00449-x

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