title: Missense mutations that alter the DNA-binding domain of the MtrR protein occur frequently in rectal isolates of Neisseria gonorrhoeae that are resistant to faecal lipids.
abstract: Resistance of Neisseria gonorrhoeae to structurally diverse hydrophobic agents (HAs) has been associated with missense or deletion mutations in the mtrR (multiple transferable resistance Regulator) gene of laboratory-derived strains but their prevalence in clinical isolates was heretofore unknown. Since faecal lipids provide strong selective pressure for the emergence of variants resistant to HAs (HAR), the nucleotide sequence of the mtrR gene from rectal isolates of N. gonorrhoeae, which displayed different levels of HAR, was determined. Compared to the mtrR gene possessed by the HA-sensitive strain FA19, each clinical isolate contained mutations in the coding and/or promoter regions of their mtrR gene. A missense mutation in codon 45 (Gly-45 to Asp) was the most common mutation found in the strains studied and impacted the structure of the helix-turn-helix domain of the MtrR protein thought to be important in DNA-binding activity. Two clinical isolates bearing a missense mutation in codon 45 also contained a single basepair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region. Introduction of mtrR sequences amplified from the clinical isolates into strain FA19 revealed that acquisition of the single basepair deletion was correlated with high level HAR while mutations in the mtrR-coding region provided for an intermediate level of HAR.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Shafer
authors.forename: J T
authors.initials: JT
authors.lastname: Balthazar
authors.forename: K E
authors.initials: KE
authors.lastname: Hagman
authors.forename: S A
authors.initials: SA
authors.lastname: Morse
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D005243:Feces / Q000737:chemistry; D005287:Ferredoxin-NADP Reductase; D005798:Genes, Bacterial; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012007:Rectum / Q000382:microbiology*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D008055:Lipids; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase