Amundsen, Susan K. and Fero, Jutta and Hansen, Lori M. and Cromie, Gareth A. and Solnick, Jay V. and Smith, Gerald R. and Salama, Nina R. (2008) Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization. Molecular microbiology, 69 (4). pp. 994-1007. ISSN 1365-2958
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Abstract
Helicobacter pylori colonization of the human stomach is characterized by profound disease-causing inflammation. Bacterial proteins that detoxify reactive oxygen species or recognize damaged DNA adducts promote infection, suggesting that H. pylori requires DNA damage-repair for successful in vivo colonization. The molecular mechanisms of repair remain unknown. We identified homologs of the AddAB class of helicase-nuclease enzymes, related to the Escherichia coli RecBCD enzyme, which, with RecA, is required for repair of DNA breaks and homologous recombination. H. pylori mutants lacking addA or addB genes lack detectable ATP-dependent nuclease activity, and the cloned H. pylori addAB genes restore both nuclease and helicase activities to an E. colirecBCD deletion mutant. H. pylori addAB and recA mutants have a reduced capacity for stomach colonization. These mutants are sensitive to DNA damaging agents and have reduced frequencies of apparent gene conversion between homologous genes encoding outer membrane proteins. Our results reveal requirements for double-strand break repair and recombination during both acute and chronic phases of H. pylori stomach infection.
| Item Type: | Article or Abstract |
|---|---|
| DOI: | 10.1111/j.1365-2958.2008.06336.x |
| PubMed ID: | 18573180 |
| NIHMSID: | NIHMS65574 |
| PMCID: | PMC2680919 |
| Grant Numbers: | R01 AI054423-05 , R56 GM031693 , R01 AI042081-09S1, FHCRC Synergy Fund |
| Keywords or MeSH Headings: | Amino Acid Sequence Animals Bacterial Proteins/genetics Bacterial Proteins/physiology* DNA Breaks, Double-Stranded DNA Helicases/genetics DNA Helicases/physiology* DNA Repair Escherichia coli/enzymology Escherichia coli/genetics Exodeoxyribonucleases/genetics Exodeoxyribonucleases/physiology* Female Helicobacter Infections/microbiology* Helicobacter pylori/enzymology Helicobacter pylori/genetics Helicobacter pylori/physiology* Mice Mice, Inbred C57BL Molecular Sequence Data Rec A Recombinases/genetics Rec A Recombinases/physiology* Recombination, Genetic Stomach/microbiology* |
| Subjects: | Diseases > Bacterial and fungal diseases Cellular and Organismal Processes > Genetic processes > DNA damage and repair Organisms > Bacteria |
| Depositing User: | Library Staff |
| Date Deposited: | 23 Sep 2008 19:45 |
| Last Modified: | 14 Feb 2012 14:42 |
| URI: | http://authors.fhcrc.org/id/eprint/17 |
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