Restricted accessResearch articleFirst published online 2011-08
Clinical Neisseria gonorrhoeae Isolates in the United States with Resistance to Azithromycin Possess Mutations in All 23S rRNA Alleles and the mtrR Coding Region
We identified strains of Neisseria gonorrhoeae in San Diego County, California, that possess high levels of resistance to azithromycin (8.0–16.0 μg/ml MIC). These isolates contain a combination of mutations in both the 23S rRNA loci and mtrR genes. This is the first description of such isolates in the United States.
Get full access to this article
View all access options for this article.
References
1.
AmeyamaS., OnoderaS., TakahataM., MinamiS., MakiN., EndoK., GotoH., SuzukiH., OishiY.2002. Mosaic-like structure of penicillin-binding protein 2 Gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob. Agents Chemother, 46:3744–3749.
2.
BarryP.M., KlausnerJ.D.2009. The use of cephalosporins for gonorrhea: the impending problem of resistance. Expert Opin. Pharmacother., 10:555–577.
3.
Centers for Disease Control, Prevention (CDC). 2007. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR, 56:332–336.
4.
Centers for Disease Control, Prevention. Sexually Transmitted Disease Surveillance, 2009Atlanta: U.S. Department of Health and Human Services, 2010.
5.
ChisholmS.A., NealT.J., AlawattegamaA.B., BirleyH.D.L., HoweR.A., IsonC.A.2009. Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales. J. Antimicrob. Chemother., 64:353–358.
6.
EhretJ.M., NimsL.J., JudsonF.N.1996. A clinical isolate of Neisseria gonorrhoeae with in vitro resistance to erythromycin and decreased susceptibility to azithroymycin. Sex. Transm. Dis., 23:270–272.
7.
GalarzaP.G., AlcaláB., SalcedoC., CanigiaL.F., BuscemiL., PaganoI., OviedoC., VázquezJ.A.2009. Emergence of high level azithromycin-resistant Neisseria gonorrhoeae strain isolated in Argentina. Sex. Transm. Dis., 36:787–788.
8.
GalarzaP.G., AbadR., CanigiaL.F., BuscemiL., PaganoI., OviedoC., VázquezJ.A.2010. New Mutation in 23S rRNA gene associated with high level of azithromycin resistance in Neisseria gonorrhoeae. Antimicrob. Agents Chemother., 54:1652–1653.
9.
HagmanK.E., ShaferW.M.1995. Transriptional control of the mtr efflux system of Neisseria gonorrhoeae. J. Bacteriol., 177:4162–4165.
10.
HoffmannK.M., WilliamsD., ShaferW.M., BrennanR.G.2005. Characterization of the multiple transferable resistance repressor, MtrR, from Neisseria gonorrhoeae. J. Bacteriol., 187:5008–5012.
11.
LucasC.E., BalthazarJ.T., HagmanK.E., ShaferW.M.1995. Importance of lipooligosaccharide structure in determining gonococcal resistance to hydrophobic antimicrobial agents resulting from the mtr efflux system. Mol. Microbiol., 16:1001–1009.
12.
MartinI.M., IsonC.A., AanensenD.M., FentonK.A., SprattB.G.2004. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J. Infect. Dis., 189:1497–1505.
13.
NgL., MartinI., LiuG., BrydenL.2002. Mutation in 23S rRNA Associated with Macrolide Resistance in Neisseria gonorrhoeae. Antimicob. Agents Chemother., 46:3020–3025.
14.
OhnishiM., WatanabeY., OnoE., TakahashiC., OyaH., KurokiT., ShimutaK., OkazakiN., NakayamaS.I., WatanabeH.2010. Spreading of a chromosomal cefixime resistant penA gene among different Neisseria gonorrhoeae lineages. Antimicrob. Agents Chemother., 54:1060–1067.
15.
PalmerH.M., YoungH., WinterA., DaveJ.2008. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J. Antimicrob. Chemother., 62:490–494.
16.
PanW., SprattB.G.1994. Regulation of the permeability of the gonococcal cell envelope by the mtr system. Mol. Microbiol., 11:769–775.
17.
PoehlsgaardJ., DouthwaiteS.2003. Macrolide antibiotic interaction and resistance on the bacterial ribosome. Curr. Opin. Investig. Drugs., 4:140–148.
18.
StarninoS., StefanelliP.Neisseria gonorrhoeae Italian Study Group. 2009. Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy. J. Antimicrob. Chemother., 63:1200–1204.
19.
SnyderL.A., McGowanS., RogersM., DuroE., O'FarrellE., SaundersN.J.2007. The repertoire of minimal mobile elements in the Neisseria species and evidence that these are involved in horizontal gene transfer in other bacteria. Mol. Biol. Evol., 24:2802–2815.
20.
SnyderL.A., ColeJ.A., PallenM.J.2009. Comparative analysis of two Neisseria gonorrhoeae genome sequences reveals evidence of mobilization of Correia Repeat Enclosed Elements and their role in regulation. B.M.C. Genomics, 10:70.
21.
WarnerD.M., ShaferW.M., JerseA.E.2008. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol. Microbiol., 70:462–478.
22.
ZarantonelliL., BorthagarayG., LeeE.H., ShaferW.M.1999. Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations. Antimicrob. Agents Chemother., 43:2468–2472.
23.
ZarantonelliL., BorthagarayG., LeeE.H., VealW., ShaferW.M.2001. Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae. J. Antimicrob. Chemother., 47:651–654.