Abstract
A
Staphylococcus aureus
strain that harbored a plasmid-borne inducibly expressed
erm
(C) gene was cultivated in the presence of the noninducers quinupristin, telithromycin, and ABT-773. After
overnight incubation, 78 mutants that displayed combined resistance to macrolides, lincosamides, streptogramin B antibiotics, and ketolides were analyzed for the genetic basis of this altered resistance
phenotype. Because this resistance phenotype is indicative for constitutively expressed
erm
(C) genes, the
erm
(C) regulatory regions of all mutants were sequenced. All 78 mutants showed sequence
alterations in the
erm
(C) translational attenuator. Seventeen different types of sequence deletions ranging from 5 bp to 121 bp and nine different types of tandem duplications of 13-100 bp, all causing
constitutive
erm
(C) gene expression, were detected. These sequence deletions or tandem duplications either favored the formation of mRNA secondary structures in the
erm
(C) translational attenuator,
which did not inhibit translation of the
erm
(C) transcripts, or completely prevented the formation of any mRNA secondary structures in the
erm
(C) translational attenuator. The mean frequencies
of 10
-6
to 10
-8
by which constitutive mutants were obtained, strongly suggest that telithromycin and ABT-773 not be recommended for the treatment of staphylococci that exhibit the
inducible MLS
B
phenotype.