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Infection and Immunity, November 2009, p. 4912-4924, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00571-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Atypical Roles for Campylobacter jejuni Amino Acid ATP Binding Cassette Transporter Components PaqP and PaqQ in Bacterial Stress Tolerance and Pathogen-Host Cell Dynamics

Ann E. Lin,¹ Kirsten Krastel,² Rhonda I. Hobb,³ Stuart A. Thompson,³ Dennis G. Cvitkovitch,² and Erin C. Gaynor^1*

Department of Microbiology and Immunology, Life Sciences Centre, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3,¹ Dental Research Institute, University of Toronto, 124 Edward St., Toronto, Ontario, M5G 1G6, Canada,² Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912³

Received 9 May 2008/ Returned for modification 7 July 2008/ Accepted 19 August 2009

Campylobacter jejuni is a human pathogen causing severe diarrheal disease; however, our understanding of the survival of C. jejuni during disease and transmission remains limited. Amino acid ATP binding cassette (AA-ABC) transporters in C. jejuni have been proposed as important pathogenesis factors. We have investigated a novel AA-ABC transporter system, encoded by cj0467 to cj0469, by generating targeted deletions of cj0467 (the membrane transport component) and cj0469 (the ATPase component) in C. jejuni 81-176. The analyses described here have led us to designate these genes paqP and paqQ, respectively (pathogenesis-associated glutamine [q] ABC transporter permease [P] and ATPase [Q]). We found that loss of either component resulted in amino acid uptake defects, most notably diminished glutamine uptake. Altered resistance to a series of environmental and in vivo stresses was also observed: both mutants were hyperresistant to aerobic and organic peroxide stress, and while the paqP mutant was also hyperresistant to heat and osmotic shock, the paqQ mutant was more susceptible than the wild type to the latter two stresses. The paqP and paqQ mutants also displayed a surprising but statistically significant increase in recovery from macrophages and epithelial cells in short-term intracellular survival assays. Annexin V, 4',6-diamidino-2-phenylindole (DAPI), and Western blot analyses revealed that macrophages infected with the paqP or paqQ mutant exhibited transient but significant decreases in cell death and extracellular signal-regulated kinase-mitogen-activated protein kinase activation compared to levels in wild-type-infected cells. The paqP mutant was not defective in either short-term or longer-term mouse colonization, consistent with its increased stress survival and diminished host cell damage phenotypes. Collectively, these results demonstrate a unique correlation of an AA-ABC transporter with bacterial stress tolerances and host cell responses to pathogen infection.

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* Corresponding author. Mailing address: The University of British Columbia, Department of Microbiology and Immunology, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada. Phone: (604) 822-2710. Fax: (604) 822-6041. E-mail: egaynor{at}interchange.ubc.ca

Published ahead of print on 24 August 2009.

Editor: V. J. DiRita

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Infection and Immunity, November 2009, p. 4912-4924, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00571-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.