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Infection and Immunity, April 2000, p. 2016-2023, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Helicobacter pylori Possesses Two CheY Response Regulators and a Histidine Kinase Sensor, CheA, Which Are Essential for Chemotaxis and Colonization of the Gastric Mucosa

Susan Foynes,1,dagger Nick Dorrell,1 Stephen J. Ward,1,Dagger Richard A. Stabler,1 Andy A. McColm,2 Andrew N. Rycroft,3 and Brendan W. Wren1,*

Pathogen Molecular Biology and Biochemistry Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London,1 Systems Biology Unit, Glaxo Wellcome Research and Development, Stevenage,2 and Veterinary Bacteriology Group, Royal Veterinary College, North Mymms,3 United Kingdom

Received 30 August 1999/Returned for modification 21 December 1999/Accepted 20 January 2000

Infection of the mucous layer of the human stomach by Helicobacter pylori requires the bacterium to be motile and presumably chemotactic. Previous studies have shown that fully functional flagella are essential for motility and colonization, but the role of chemotaxis remains unclear. The two-component regulatory system CheA/CheY has been shown to play a major role in chemotaxis in other enteric bacteria. Scrutiny of the 26695 genome sequence suggests that H. pylori has two CheY response regulators: one a separate protein (CheY1) and the other (CheY2) fused to the histidine kinase sensor CheA. Defined deletion mutations were introduced into cheY1, cheY2, and cheA in H. pylori strains N6 and SS1. Video tracking revealed that the wild-type H. pylori strain moves in short runs with frequent direction changes, in contrast to movement of cheY2, cheAY2, and cheAY2 cheY1 mutants, whose motion was more linear. The cheY1 mutant demonstrated a different motility phenotype of rapid tumbling. All mutants had impaired swarming and greatly reduced chemotactic responses to hog gastric mucin. Neither cheY1 nor cheAY2 mutants were able to colonize mice, but they generated a significant antibody response, suggesting that despite impaired chemotaxis, these mutants were able to survive in the stomach long enough to induce an immune response before being removed by gastric flow. Additionally, we demonstrated that cheY1 failed to colonize gnotobiotic piglets. This study demonstrates the importance of the roles of cheY1, cheY2, and cheA in motility and virulence of H. pylori.

* Corresponding author. Mailing address: Pathogen Molecular Biology and Biochemistry Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 44 (0)171 927 2288. Fax: 44 (0)171 636 8739. E-mail: brendan.wren{at}lshtm.ac.uk.

dagger Present address: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.

Dagger Present address: Medeva Development, Vaccine Research Unit, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.

Infection and Immunity, April 2000, p. 2016-2023, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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