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Infection and Immunity, April 2003, p. 2022-2031, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2022-2031.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Helicobacter pylori Mutants Defective in RuvC Holliday Junction Resolvase Display Reduced Macrophage Survival and Spontaneous Clearance from the Murine Gastric Mucosa

Michael F. Loughlin,1 Faye M. Barnard,1 David Jenkins,2 Gary J. Sharples,3 and Peter J. Jenks1*

Institute of Infections and Immunity,1 Division of Pathology, University of Nottingham, Nottingham,2 Department of Biological Sciences, University of Durham, Durham, United Kingdom3

Received 7 October 2002/ Returned for modification 14 November 2002/ Accepted 11 December 2002

Homologous recombination contributes to the extraordinary genetic diversity of Helicobacter pylori and may be critical for surface antigen expression and adaptation to environmental challenges within the stomach. We generated isogenic, nonpolar H. pylori ruvC mutants to investigate the function of RuvC, a Holliday junction endonuclease that resolves recombinant joints into nicked duplex products. Inactivation of ruvC reduced the frequency of homologous recombination of H. pylori between 17- and 45-fold and increased sensitivity to DNA-damaging agents and the antimicrobial agents levofloxacin and metronidazole. The H. pylori ruvC mutants were more susceptible to oxidative stress and exhibited reduced survival within macrophages. Experiments with the H. pylori SS1 mouse model revealed that the 50% infective dose of the ruvC mutant was approximately 100-fold higher than that of the wild-type SS1 strain. Although the ruvC mutant was able to establish colonization with bacterial loads that were initially similar to those of the parental SS1 strain, infection was spontaneously cleared from the murine gastric mucosa over periods that varied from 36 to 67 days. These results demonstrate that, in this infection model, RuvC is essential for continued survival of H. pylori in vivo and raises the possibility that inactivation of ruvC might be of value in an attenuated vaccine strain.

* Corresponding author. Mailing address: Institute of Infections and Immunity, Floor C, West Block, University Hospital, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom. Phone: 44-115-924-9924, ext. 42457. Fax: 44-115-970-9923. E-mail: Peter.Jenks{at}nottingham.ac.uk.

Editor: D. L. Burns

Infection and Immunity, April 2003, p. 2022-2031, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2022-2031.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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