Affiliation:
1. Sexually Transmitted Bacteria Reference Laboratory, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, Colindale, London NW9 5HT
2. Scottish Bacterial Sexually Transmitted Infections Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
Abstract
ABSTRACT
High-level azithromycin resistance (AZM-HR), defined as a MIC of ≥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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
163 articles.
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