Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae

• Published in: Microbiology (Society for General Microbiology) 1998-03, Vol.144 (3), p.621-627
• Main Authors: Veal, Wendy L, Yellen, Ansley, Balthazar, Jacqueline T, Pan, Wubin, Spratt, Brian G, Shafer, William M
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacterial Outer Membrane Proteins - genetics; Bacterial Proteins; Bacteriology; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Drug Resistance, Microbial; Drug Resistance, Multiple - genetics; Ferredoxin-NADP Reductase; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gene Deletion; Genetics; Humans; Lipoproteins - genetics; Membrane Proteins - genetics; Membrane Transport Proteins; Microbiology; Molecular Sequence Data; Neisseria gonorrhoeae; Neisseria gonorrhoeae - drug effects; Neisseria gonorrhoeae - genetics; Neisseria gonorrhoeae - metabolism; Operon; Repressor Proteins - genetics; Sequence Analysis, DNA; Species Specificity; Suppression, Genetic; Transformation, Bacterial
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/00221287-144-3-621

1 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA 2 Microbial Genetics Group, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK 3 Laboratories of Microbial Pathogenesis, Medical Research Service, VA Medical Center (Atlanta), Decatur, GA 30033, USA 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. Author for correspondence: William M. Shafer. Tel: [phone]. Fax: + 1 404 329 2210. e-mail: [e-mail] Keywords: gonococci, efflux pump, antibiotic hypersusceptibility Present address: TerraGen Diversity Inc., University of British Columbia, Vancouver, Canada V6T 123. Present address: Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, Oxford University, South Parks Road, Oxford OX1 3PS, UK.