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The role of ribosomal RNAs in macrolide resistance
Author(s) -
Sander Peter,
Prammananan Therdsak,
Meier Albrecht,
Frischkorn Klaus,
Böttger Erik C.
Publication year - 1997
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1997.5811946.x
Subject(s) - biology , operon , 23s ribosomal rna , ribosomal rna , mycobacterium smegmatis , genetics , gene , transfer rna , point mutation , ribosome , rna , mutation , mutant , mycobacterium tuberculosis , tuberculosis , medicine , pathology
Macrolides are bacteriostatic antibiotics which interfere with the peptidyltransfer function of the ribosome. We have investigated the molecular mechanisms underlying macrolide resistance in Mycobacterium smegmatis , an eubacterium carrying two rRNA operons. Surprisingly, drug resistance was associated not with alterations in ribosomal proteins, but with a single point mutation in the peptidyltransferase region of one of the two 23S RNA genes, i.e. A2058→G or A2059→G. This mutation resulted in a heterozygous organism with a mutated and a wild‐type rRNA operon respectively. Reverse transcriptase sequencing indicated the expression of both wild‐type and mutated rRNAs. The mutated operon was introduced into genetically engineered rrn − strains of M. smegmatis carrying a single functional rRNA operon and into parental M. smegmatis with two chromosomal rRNA operons, using gene transfer as well as gene replacement techniques. The results obtained demonstrate the dominant nature of resistance. As exemplified in our results on macrolide resistance, a complete set of genetic tools is now available, which allows questions of dominance vs. recessivity and gene dosage effects in eubacterial ribosomal nucleic acids to be addressed experimentally in vivo .