title: Regulation of mtrF expression in Neisseria gonorrhoeae and its role in high-level antimicrobial resistance.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Folster
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D016384:Consensus Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C094589:MtrC protein, Neisseria gonorrhoeae; C107795:MtrD protein, Neisseria gonorrhoeae; C107796:MtrE protein, Neisseria gonorrhoeae; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae