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Mutations causing in vitro resistance to azithromycin in Neisseria gonorrhoeae.
International Journal of Antimicrobial Agents 2003;21-:414-419.
Johnson SR, Sandul AL, Parekh M, Wang SA, Knapp JS, Tress DL.
Abstract
In 1999, a cluster of gonococcal isolates exhibiting high Minimal Inhibitory
Concentrations (MICs), to azithromycin (2.0-4.0 mg/l) were identified in
Kansas City, MO. Isolates were characterized by auxotype/serovar class, lipoprotein
(Lip) subtyping and sequencing of the mtrR gene, which has been implicated
in decreased azithromycin susceptibility in the gonococcus. Isolates were
Pro/IB-3 and contained the 17c Lip subtype. Molecular characterization of
the mtrR gene revealed a 153 base pair insertion sequence located between
the mtrR/mtrC promoter and the mtrC gene. Some isolates also contained a
frame shift within the mtrR gene. Transformation of these mutations into
an azithromycin-sensitive recipient strain resulted in transformants with
MICs as high as 2.0 mg/l and inactivation of the mtrD gene reduced azithromycin
MICs 270-fold. These results demonstrated that the mtr mutations were responsible
for the increased MICs in these isolates.