Mutation in 23S rRNA Associated with Macrolide Resistance in Neisseria gonorrhoeae

Abstract

ABSTRACT Fifty-six azithromycin-resistant (MICs, 2.0 to 4.0 μg/ml) Neisseria gonorrhoeae strains with cross-resistance to erythromycin (MICs, 2.0 to 64.0 μg/ml), isolated in Canada between 1997 and 1999, were characterized, and their mechanisms of azithromycin resistance were determined. Most (58.9%) of them belonged to auxotype-serotype class NR/IB-03, with a 2.6-mDa plasmid. Based on resistance to crystal violet (MICs ≥ 1 μg/ml), 96.4% of these macrolide-resistant strains appeared to have increased efflux. Nine of the eleven strains selected for further characterization were found to have a promoter region mtrR mutation, a single-base-pair (A) deletion in the 13-bp inverted repeat, which is believed to cause overexpression of the mtrCDE -encoded efflux pump. The two remaining macrolide-resistant strains (erythromycin MIC, 64.0 μg/ml; azithromycin MIC, 4.0 μg/ml), which did not have the mutation in the mtrR promoter region, were found to have a C2611T mutation ( Escherichia coli numbering) in the peptidyltransferase loop in domain V of the 23S rRNA alleles. Although mutations in domain V of 23S rRNA alleles had been reported in other bacteria, including E. coli , Streptococcus pneumoniae , and Helicobacter pylori , this is the first observation of these mutations associated with macrolide resistance in N. gonorrhoeae .