title: Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae.
abstract: Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents (HAs) has been ascribed to the mtr (multiple transferable resistance) operon. This operon is composed of the mtrR gene, which encodes a transcriptional repressor (MtrR), and a three-gene complex (mtrCDE), which encodes cell envelope proteins (MtrC-MtrD-MtrE) that form an energy-dependent efflux pump. HA-hypersusceptible strains are often isolated from patients, but the genetic basis for such hypersusceptibility was heretofore unknown. The genetic basis of HA hypersusceptibility in laboratory-derived strains BR54 and BR87 was studied to learn if this trait could be linked to mutations in the mtr operon. Mutations in the mtrR gene of these strains that could be phenotypically suppressed by mutations in their mtrC or mtrD genes were identified. Thus, small deletions (4-10 bp) in the mtrC or mtrD genes of strains BR87 and BR54 that would result in the production of truncated efflux pump proteins that serve as a membrane fusion protein (MtrC) or transporter of HAs (MtrD) were found to be responsible for their HA-hypersusceptible property.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine,Atlanta, GA 30322, USA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Veal
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine,Atlanta, GA 30322, USA.
authors.forename: Ansley
authors.initials: A
authors.lastname: Yellen
authors.affiliation: Laboratories of Microbial Pathogenesis, Medical Research Service, VA Medical Center (Atlanta),Decatur, GA 30033,USA.|Department of Microbiology and Immunology, Emory University School of Medicine,Atlanta, GA 30322, USA.
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Balthazar
authors.affiliation: Microbial Genetics Group, School of Biological Sciences, University of Sussex,Falmer, Brighton BN1 9QG,UK.
authors.forename: Wubin
authors.initials: W
authors.lastname: Pan
authors.affiliation: Microbial Genetics Group, School of Biological Sciences, University of Sussex,Falmer, Brighton BN1 9QG,UK.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.affiliation: Laboratories of Microbial Pathogenesis, Medical Research Service, VA Medical Center (Atlanta),Decatur, GA 30033,USA.|Department of Microbiology and Immunology, Emory University School of Medicine,Atlanta, GA 30322, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005287:Ferredoxin-NADP Reductase; D005784:Gene Amplification; D017353:Gene Deletion; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009876:Operon; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013489:Suppression, Genetic; D014169:Transformation, Bacterial
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier 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; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase