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Infection and Immunity, March 2007, p. 1318-1324, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01530-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lactate Acquisition Promotes Successful Colonization of the Murine Genital Tract by Neisseria gonorrhoeae{triangledown}

Rachel M. Exley,1,{dagger} Hong Wu,2,{dagger} Jonathan Shaw,3 Muriel C. Schneider,1 Harry Smith,4 Ann E. Jerse,2* and Christoph M. Tang1*

The Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Flowers Building, Imperial College London, Armstrong Road, London SW7 2AZ, United Kingdom,1 Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland 20814,2 Division of Genomic Medicine, F-floor, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom,3 The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom4

Received 22 September 2006/ Returned for modification 4 November 2006/ Accepted 29 November 2006

Previous studies on Neisseria gonorrhoeae have demonstrated that metabolism of lactate in the presence of glucose increases the growth rate of the bacterium and enhances its resistance to complement-mediated killing. Although these findings in vitro suggest that the acquisition of lactate promotes gonococcal colonization, the significance of this carbon source to the survival of the gonococcus in vivo remains unknown. To investigate the importance of lactate utilization during Neisseria gonorrhoeae genital tract infection, we identified the gene lctP, which encodes the gonococcal lactate permease. A mutant that lacks a functional copy of lctP was unable to take up exogenous lactate and did not grow in defined medium with lactate as the sole carbon source, in contrast to the wild-type and complemented strains; the mutant strain exhibited no growth defect in defined medium containing glucose. In defined medium containing physiological concentrations of lactate and glucose, the lctP mutant demonstrated reduced early growth and increased sensitivity to complement-mediated killing compared with the wild-type strain; the enhanced susceptibility to complement was associated with a reduction in lipopolysaccharide sialylation of the lctP mutant. The importance of lactate utilization during colonization was evaluated in the murine model of lower genital tract infection. The lctP mutant was significantly attenuated in its ability to colonize and survive in the genital tract, while the complemented mutant exhibited no defect for colonization. Lactate is a micronutrient in the genital tract that contributes to the survival of the gonococcus.


* Corresponding author. Mailing address for Christoph M. Tang: The Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Flowers Building, Imperial College London, Armstrong Road, London SW7 2AZ, United Kingdom. Phone: 44 20 7594 3072. Fax: 44 20 7594 3076. E-mail: c.tang{at}imperial.ac.uk. Mailing address for Ann E. Jerse: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814. Phone: (301) 295-9629. Fax: (301) 295-3773. E-mail: ajerse{at}usuhs.mil.

{triangledown} Published ahead of print on 11 December 2006.

Editor: A. Camilli

{dagger} These authors contributed equally to this work.


Infection and Immunity, March 2007, p. 1318-1324, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01530-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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