Helicobacter pylori genome evolution during human infection

Edited by Rino Rappuoli, Novartis Vaccines, Siena, Italy, and approved January 22, 2011 (received for review December 13, 2010)
March 7, 2011
108 (12) 5033-5038

Abstract

High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals = 3–16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27–232 isolated SNPs and 16–441 imported clusters of polymorphisms resulting from recombination. Imports (mean length = 394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.

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Data Availability

Data deposition: The sequences reported in this paper have been deposited in the GenBank database as whole genome shotgun projects with 12 project IDs CADC00000000 to CADN00000000 in alphabetical order. Virtual genomes have been deposited online at http://www.mh-hannover.de/20611.html.

Acknowledgments

We thank Birgit Brenneke, Friederike Kops, Jessika Schulze, and Stella Lamprecht for excellent technical assistance. Support was provided by the German Research Foundation as PhD stipends in the International Research Training Group 1273 (to L.K. and S.K.) as well as Grants SFB 900/A1 (to S.S.) and Ae16/4-4 (to T.A. and T.F.M.). Further support was provided by European Union 6th Research Framework Programme, Project Infections and Cancer (INCA) Grant LSHC-CT-2005-018704 (to T.F.M. and S.S.), and German Ministry for Education and Research ERA-NET PathoGenoMics Project HELDIVNET (to S.S.). The field work in Colombia was supported by National Cancer Institute, National Institutes of Health Grant P01CA028842 (to P.C.), and D.F. was supported by Science Foundation of Ireland Grant 05/FE1/B882 to Mark Achtman.

Supporting Information

Appendix (PDF)
Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 108 | No. 12
March 22, 2011
PubMed: 21383187

Classifications

Data Availability

Data deposition: The sequences reported in this paper have been deposited in the GenBank database as whole genome shotgun projects with 12 project IDs CADC00000000 to CADN00000000 in alphabetical order. Virtual genomes have been deposited online at http://www.mh-hannover.de/20611.html.

Submission history

Published online: March 7, 2011
Published in issue: March 22, 2011

Keywords

  1. comparative genomics
  2. mutation

Acknowledgments

We thank Birgit Brenneke, Friederike Kops, Jessika Schulze, and Stella Lamprecht for excellent technical assistance. Support was provided by the German Research Foundation as PhD stipends in the International Research Training Group 1273 (to L.K. and S.K.) as well as Grants SFB 900/A1 (to S.S.) and Ae16/4-4 (to T.A. and T.F.M.). Further support was provided by European Union 6th Research Framework Programme, Project Infections and Cancer (INCA) Grant LSHC-CT-2005-018704 (to T.F.M. and S.S.), and German Ministry for Education and Research ERA-NET PathoGenoMics Project HELDIVNET (to S.S.). The field work in Colombia was supported by National Cancer Institute, National Institutes of Health Grant P01CA028842 (to P.C.), and D.F. was supported by Science Foundation of Ireland Grant 05/FE1/B882 to Mark Achtman.

Notes

*This Direct Submission article had a prearranged editor.

Authors

Affiliations

Lynn Kennemann
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany;
Xavier Didelot
Department of Statistics, University of Oxford, Oxford OX1 1TG, United Kingdom;
Toni Aebischer
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;
Stefanie Kuhn
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany;
Bernd Drescher
GenDoc.Info UG, 10585 Berlin, Germany;
Marcus Droege
Roche Diagnostics GmbH, 82377 Penzberg, Germany;
Richard Reinhardt
Genome Center Cologne, Max Planck Institute for Plant Breeding Research, 50829 Köln, Germany;
Pelayo Correa
Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232; and
Thomas F. Meyer
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;
Christine Josenhans
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany;
Daniel Falush
Environmental Research Institute and Department of Microbiology, University College, Cork, Ireland
Present address: Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
Sebastian Suerbaum2 [email protected]
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany;
Present address: Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.

Notes

2
To whom correspondence should be addressed. E-mail: [email protected].
Author contributions: L.K., X.D., T.A., and S.S. designed research; L.K., T.A., S.K., R.R., and S.S. performed research; X.D., T.A., M.D., P.C., T.F.M., C.J., and D.F. contributed new reagents/analytic tools; L.K., X.D., S.K., B.D., C.J., D.F., and S.S. analyzed data; and L.K., X.D., and S.S. wrote the paper.

Competing Interests

Conflict of interest statement: M.D. is an employee of Roche Diagnostics GmbH.

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    Helicobacter pylori genome evolution during human infection
    Proceedings of the National Academy of Sciences
    • Vol. 108
    • No. 12
    • pp. 4697-5139

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