Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens.
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.
Pernodet
J L
JL
Laboratoire de Biologie et Génétique Moléculaire, U.A.C.N.R.S. 040086, Université Paris-Sud, Orsay, France.
Boccard
F
F
Alegre
M T
MT
Blondelet-Rouault
M H
MH
Guérineau
M
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D004352:Drug Resistance, Microbial; D005798:Genes, Bacterial; D007783:Lactones / Q000494:pharmacology; D055231:Lincosamides; D018942:Macrolides; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D012335:RNA, Ribosomal / Q000235:genetics*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics*; D014769:Virginiamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D007783:Lactones; D055231:Lincosamides; D018942:Macrolides; D012335:RNA, Ribosomal; D012338:RNA, Ribosomal, 23S; D014769:Virginiamycin; C002018:chalcomycin; D004262:DNA Restriction Enzymes