Mutations causing in vitro resistance to azithromycin in Neisseria gonorrhoeae

Int J Antimicrob Agents. 2003 May;21(5):414-9. doi: 10.1016/s0924-8579(03)00039-6.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azithromycin / pharmacology*
  • Bacterial Proteins*
  • Base Sequence
  • Drug Resistance, Bacterial / genetics*
  • Ferredoxin-NADP Reductase*
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / genetics*
  • Operon / genetics
  • Phenotype
  • Repressor Proteins / genetics
  • Transformation, Bacterial


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Proteins
  • MtrD protein, Neisseria gonorrhoeae
  • Repressor Proteins
  • mtrR protein, Neisseria gonorrhoeae
  • Azithromycin
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase