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Infection and Immunity, October 2003, p. 5576-5582, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5576-5582.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Gonococcal Efflux Pump System Enhances Bacterial Survival in a Female Mouse Model of Genital Tract Infection

Ann E. Jerse,^1* Nirmala D. Sharma,^1, Amy N. Simms,¹ Emily T. Crow,¹ Lori A. Snyder,^2, and William M. Shafer^2,3

Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland 20814,¹ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,² Medical Research Service, VA Medical Center, Decatur, Georgia 30322³

Received 7 March 2003/ Returned for modification 17 April 2003/ Accepted 14 July 2003

Active efflux of antimicrobial substances is likely to be an important bacterial defense against inhibitory host factors inherent to different body sites. Two well-characterized multidrug resistance efflux systems (MtrCDE and FarAB-MtrE) exist in Neisseria gonorrhoeae, a bacterial pathogen of the human genital mucosae. In vitro studies suggest that the MtrCDE and FarAB-MtrE efflux systems protect the gonococcus from hydrophobic antimicrobial substances that are likely to be present on mucosal surfaces. Here we report that a functional MtrCDE efflux system, but not a functional FarAB-MtrE system, enhances experimental gonococcal genital tract infection in female mice. Specifically, the recovery of mtrD and mtrE mutants, but not a farB mutant, from mice inoculated with mutant or wild-type gonococci was reduced compared with that of the wild-type strain. Competitive-infection experiments confirmed the survival disadvantage of MtrCDE-deficient gonococci. This report is the first direct evidence that a multidrug resistance efflux system enhances survival of a bacterial pathogen in the genital tract. Additionally, experiments using ovariectomized mice showed that MtrCDE-deficient gonococci were more rapidly cleared from mice that were capable of secreting gonadal hormones. MtrCDE-deficient gonococci were more sensitive to nonphysiological concentrations of progesterone in vitro than were wild-type or FarAB-MtrE-deficient gonococci. These results suggest that progesterone may play an inhibitory role in vivo. However, hormonally regulated factors rather than progesterone itself may be responsible for the more rapid clearance of mtr-deficient gonococci from intact mice.

Editor: J. N. Weiser

Present address: Laboratory of Immunobiology, National Cancer Institute at Frederick, Frederick, MD 21702.

Present address: The Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom OX1 3RE.

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