Mechanisms of resistance were studied in 22 @entity7646 -resistant mutants selected in vitro from 5 parental strains of @entity7646 -susceptible @entity328 by serial passage in various macrolides (T. A. Davies, B. E. Dewasse, M. R. Jacobs, and P. C. Appelbaum, Antimicrob. Agents Chemother., 44:414-417, 2000). Portions of genes encoding ribosomal proteins L22 and L4 and 23S rRNA (domains II and V) were amplified by PCR and analyzed by single-strand conformational polymorphism analysis to screen for mutations. The DNA sequences of amplicons from mutants that differed from those of parental strains by their electrophoretic migration profiles were determined. In six mutants, point mutations were detected in the L22 gene ( @entity69407 , @entity69408 , @entity69409 , @entity65010 , and @entity69410 ). The only mutant selected by @entity23315 (for which the MIC increased from 0.008 to 0.25 microg/ml) contained a combination of three mutations in the L22 gene ( @entity69409 , @entity65010 , and @entity69410 ). L22 mutations were combined with an L4 mutation ( @entity6905 ) in one strain and with a 23S rRNA mutation ( @entity69411 ) in another strain. Nine other strains selected by various macrolides had @entity40781 (n = 1), A2058U (n = 2), @entity40782 (n = 1), C2610U (n = 1), and C2611U (n = 4) mutations ( @entity526 numbering) in domain V of 23S rRNA. One mutant selected by @entity4581 and resistant to all macrolides tested (MIC, >32 microg/ml) and @entity23315 (MIC, 4 microg/ml) had a single base deletion (A752) in domain II. In six remaining mutants, no mutations in L22, L4, or 23S rRNA could be detected.

Diversity of ribosomal mutations conferring resistance to macrolides, clindamycin, streptogramin, and XXXX in @entity328 .

@entity7646 :: ('CHEBI:25106', 'Chemical') :: ['macrolide'] @entity65010 :: ('p|SUB|P|91|S', 'ProteinMutation') :: ['P91S'] @entity4581 :: ('MESH:D017291', 'Chemical') :: ['clarithromycin'] @entity69407 :: ('p|SUB|G|95|D', 'ProteinMutation') :: ['G95D'] @entity69410 :: ('p|SUB|G|83|E', 'ProteinMutation') :: ['G83E'] @entity40782 :: ('c|SUB|A|2059|G', 'DNAMutation') :: ['A2059G'] @entity40781 :: ('c|SUB|A|2058|G', 'DNAMutation') :: ['A2058G'] @entity69408 :: ('p|SUB|P|99|Q', 'ProteinMutation') :: ['P99Q'] @entity69409 :: ('p|SUB|A|93|E', 'ProteinMutation') :: ['A93E'] @entity23315 :: ('MESH:C106791', 'Chemical') :: ['telithromycin'] @entity6905 :: ('p|SUB|G|71|R', 'ProteinMutation') :: ['G71R'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae'] @entity526 :: ('562', 'Species') :: ['Escherichia coli'] @entity69411 :: ('c|SUB|C|2611|A', 'DNAMutation') :: ['C2611A']
@entity23315 :: (MESH:C106791,Chemical) :: ['telithromycin']
