Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens

EMBO J. 1988 Jan;7(1):277-82.

Abstract

Streptomyces ambofaciens produces spiramycin, a macrolide antibiotic and expresses an inducible resistance to macrolides, lincosamides and streptogramin B antibiotics (MLS). From a mutant of S.ambofaciens exhibiting a constitutive MLS resistance phenotype a resistance determinant was cloned on a low copy number vector (pIJ61) through its expression in Streptomyces lividans. Further characterization has shown that this determinant corresponded to a mutant rRNA operon with a mutation in the 23S rRNA gene. In different organisms, mutations leading to MLS resistance have been located at a position corresponding to the adenine 2058 of Escherichia coli 23S rRNA. In the 23S rRNA from S.ambofaciens a similar position for the mutation has been postulated and DNA sequencing of this region has shown an adenine to guanine transition at a position corresponding to 2058. S.ambofaciens possesses four rRNA operons which we have cloned. In Streptomyces, contrary to other bacteria, a mutation in one among several rRNA operons confers a selectable MLS resistance phenotype. Possible reasons for this difference are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Base Sequence
  • Cloning, Molecular
  • DNA Restriction Enzymes
  • Drug Resistance, Microbial
  • Genes, Bacterial*
  • Lactones / pharmacology
  • Lincosamides
  • Macrolides*
  • Molecular Sequence Data
  • Mutation*
  • Operon*
  • RNA, Ribosomal / genetics*
  • RNA, Ribosomal, 23S / genetics
  • Streptomyces / drug effects
  • Streptomyces / genetics*
  • Virginiamycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Lactones
  • Lincosamides
  • Macrolides
  • RNA, Ribosomal
  • RNA, Ribosomal, 23S
  • Virginiamycin
  • chalcomycin
  • DNA Restriction Enzymes