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Journal of Bacteriology, February 2003, p. 1101-1106, Vol. 185, No. 3
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.3.1101-1106.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The NorM Efflux Pump of Neisseria gonorrhoeae and Neisseria meningitidis Recognizes Antimicrobial Cationic Compounds

Corinne Rouquette-Loughlin,1 Steven A. Dunham,2 Michael Kuhn,2 Jacqueline T. Balthazar,1 and William M. Shafer1,3*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,1 Antibacterial Molecular Sciences, Ann Arbor Laboratories, Pfizer Global Research and Development, Ann Arbor, Michigan 48105,2 Laboratories of Microbial Pathogenesis, VA Medical Center, Decatur, Georgia 300333

Received 10 July 2002/ Accepted 1 November 2002

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 728-7688. Fax: (404) 329-2210. E-mail: wshafer{at}emory.edu.

Journal of Bacteriology, February 2003, p. 1101-1106, Vol. 185, No. 3
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.3.1101-1106.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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