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Journal of Bacteriology, June 2005, p. 3713-3720, Vol. 187, No. 11
0021-9193/05/$08.00+0     doi:10.1128/JB.187.11.3713-3720.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Regulation of mtrF Expression in Neisseria gonorrhoeae and Its Role in High-Level Antimicrobial Resistance

Jason P. Folster1,2 and William M. Shafer1,2*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,1 Laboratories of Microbial Pathogenesis, Veterans Affairs Medical Center, Decatur, Georgia 300332

Received 27 January 2005/ Accepted 2 March 2005

The obligate human pathogen Neisseria gonorrhoeae uses the MtrC-MtrD-MtrE efflux pump to resist structurally diverse hydrophobic antimicrobial agents (HAs), some of which bathe mucosal surfaces that become infected during transmission of gonococci. Constitutive high-level HA resistance occurs by the loss of a repressor (MtrR) that negatively controls transcription of the mtrCDE operon. This high-level HA resistance also requires the product of the mtrF gene, which is located downstream and transcriptionally divergent from mtrCDE. MtrF is a putative inner membrane protein, but its role in HA resistance mediated by the MtrC-MtrD-MtrE efflux pump remains to be determined. High-level HA resistance can also be mediated through an induction process that requires enhanced transcription of mtrCDE when gonococci are grown in the presence of a sublethal concentration of Triton X-100. We now report that inactivation of mtrF results in a significant reduction in the induction of HA resistance and that the expression of mtrF is enhanced when gonococci are grown under inducing conditions. However, no effect was observed on the induction of mtrCDE expression in an MtrF-negative strain. The expression of mtrF was repressed by MtrR, the major repressor of mtrCDE expression. In addition to MtrR, another repressor (MpeR) can downregulate the expression of mtrF. Repression of mtrF by MtrR and MpeR was additive, demonstrating that the repressive effects mediated by these regulators are independent processes.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 728-7688. Fax: (404) 329-2210. E-mail: wshafer{at}emory.edu.


Journal of Bacteriology, June 2005, p. 3713-3720, Vol. 187, No. 11
0021-9193/05/$08.00+0     doi:10.1128/JB.187.11.3713-3720.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Folster, J. P., Johnson, P. J. T., Jackson, L., Dhulipali, V., Dyer, D. W., Shafer, W. M. (2009). MtrR Modulates rpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae. J. Bacteriol. 191: 287-297 [Abstract] [Full Text]  
  • Garvin, L. E., Bash, M. C., Keys, C., Warner, D. M., Ram, S., Shafer, W. M., Jerse, A. E. (2008). Phenotypic and Genotypic Analyses of Neisseria gonorrhoeae Isolates That Express Frequently Recovered PorB PIA Variable Region Types Suggest that Certain P1a Porin Sequences Confer a Selective Advantage for Urogenital Tract Infection. Infect. Immun. 76: 3700-3709 [Abstract] [Full Text]  
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