Mutations causing in vitro resistance to azithromycin in Neisseria gonorrhoeae.
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.
Gonorrhea Research Branch, Division of AIDS, STD and TB Laboratory Research, NCID, Mailstop C-13, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
Steven R
SR
Johnson
Amy L
AL
Sandul
Manhar
M
Parekh
Susan A
SA
Wang
Joan S
JS
Knapp
David L
DL
Trees
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001426:Bacterial Proteins; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005287:Ferredoxin-NADP Reductase; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics*; D009876:Operon / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D014169:Transformation, Bacterial; D026901:Membrane Transport Proteins
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D001426:Bacterial Proteins; D005287:Ferredoxin-NADP Reductase; D008565:Membrane Proteins; D012097:Repressor Proteins; C107795:MtrD protein, Neisseria gonorrhoeae; D026901:Membrane Transport Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; C111241:methionine synthase reductase