title: The NorM efflux pump of Neisseria gonorrhoeae and Neisseria meningitidis recognizes antimicrobial cationic compounds.
abstract: In Neisseria gonorrhoeae and Neisseria meningitidis, we identified a gene that would encode a protein highly similar to NorM of Vibrio parahaemolyticus (Y. Morita et al., Antimicrob. Agents Chemother. 42:1778-1782, 1998). A nonpolar insertional mutation in either the gonococcal or meningococcal norM gene resulted in increased bacterial sensitivity to compounds harboring a quaternary ammonium on an aromatic ring (e.g., ethidium bromide, acriflavine hydrochloride, 2-N-methylellipticinium, and berberine). The presence of point mutations within the -35 region of a putative norM promoter or a likely ribosome binding site resulted in an increased resistance of gonococci and meningococci to the same compounds, as well as to norfloxacin and ciprofloxacin. Structure-activity relationship studies with putative NorM substrates have found that a cationic moiety is essential for NorM recognition.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Rouquette-Loughlin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Dunham
authors.forename: Michael
authors.initials: M
authors.lastname: Kuhn
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Balthazar
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D000595:Amino Acid Sequence; D017920:Antiporters / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D001426:Bacterial Proteins; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects*; D009345:Neisseria meningitidis / Q000187:drug effects*; D009643:Norfloxacin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; C114619:NorM protein, bacteria; D002939:Ciprofloxacin; D009643:Norfloxacin