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High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2010 Sep; Vol. 54 (9), pp. 3812-6. Date of Electronic Publication: 2010 Jun 28. - Publication Year :
- 2010
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Abstract
- High-level azithromycin resistance (AZM-HR), defined as a MIC of > or = 256 mg/liter, emerged in Neisseria gonorrhoeae in the United Kingdom in 2004. To determine the mechanism of this novel phenotype, isolates from the United Kingdom that were AZM-HR (n, 19), moderately AZM resistant (MICs, 2 to 8 mg/liter) (n, 26), or sensitive (MICs, 0.12 to 0.25 mg/liter) (n, 4) were screened for methylase (erm) genes and for mutations in the mtrR promoter region, associated with efflux pump upregulation. All AZM-resistant isolates and 12 sensitive isolates were screened for mutations in domain V of each 23S rRNA allele. All AZM-HR isolates contained the A2059G mutation (Escherichia coli numbering) in three (3 isolates) or four (16 isolates) 23S rRNA alleles. Most (22/26) moderately AZM resistant isolates contained the C2611T mutation in at least 3/4 alleles. The remainder contained four wild-type alleles, as did 8/12 sensitive isolates, while one allele was mutated in the remaining four sensitive isolates. Serial passage of AZM-sensitive colonies on an erythromycin-containing medium selected AZM-HR if the parent strain already contained mutation A2059G in one 23S rRNA allele. The resultant AZM-HR strains contained four mutated alleles. Eight isolates (five moderately AZM resistant and three AZM-HR) contained mutations in the mtrR promoter. No methylase genes were detected. This is the first evidence that AZM-HR in gonococci may result from a single point mutation (A2059G) in the peptidyltransferase loop in domain V of the 23S rRNA gene. Mutation of a single allele is insufficient to confer AZM-HR, but AZM-HR can develop under selection pressure. The description of a novel resistance mechanism will aid in screening for the AZM-HR phenotype.
- Subjects :
- Bacterial Proteins genetics
Drug Resistance, Bacterial genetics
Polymerase Chain Reaction
Promoter Regions, Genetic genetics
Repressor Proteins genetics
Anti-Bacterial Agents pharmacology
Azithromycin pharmacology
Neisseria gonorrhoeae drug effects
Neisseria gonorrhoeae genetics
Point Mutation genetics
RNA, Ribosomal, 23S genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 54
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 20585125
- Full Text :
- https://doi.org/10.1128/AAC.00309-10