Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization.
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 homologues 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. coli recBCD 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.
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Susan K
SK
Amundsen
Jutta
J
Fero
Lori M
LM
Hansen
Gareth A
GA
Cromie
Jay V
JV
Solnick
Gerald R
GR
Smith
Nina R
NR
Salama
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005260:Female; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011938:Rec A Recombinases / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D013270:Stomach / Q000382:microbiology*
D001426:Bacterial Proteins; D011938:Rec A Recombinases; D005090:Exodeoxyribonucleases; C407424:AddAB enzyme; D004265:DNA Helicases