title: Resistance to macrolides in clinical isolates of Streptococcus pyogenes due to ribosomal mutations.
abstract: OBJECTIVE
  Two clinical strains of Streptococcus pyogenes, 237 and 544, one isolated in Slovakia and the other in Croatia, that were resistant to azithromycin (MIC 8 and 2 mg/L, respectively) but susceptible to erythromycin (MIC 0.5 and 0.12 mg/L, respectively) did not contain any gene known to confer macrolide resistance by ribosomal modification (erm gene) or efflux [mef(A) and msr(A) genes]. The aim of the study was to determine the mechanisms of macrolide resistance in both strains.
  
  
  METHODS
  Portions of genes encoding ribosomal proteins L22 and L4, and 23S rRNA (domains II and V) in the two macrolide-resistant strains and in control strains susceptible to macrolides, were analysed by PCR and single-strand conformational polymorphism, to screen for mutations. The DNA sequences of amplicons from resistant strains that differed from those of susceptible strains, in terms of their electrophoretic migration profiles, were determined.
  
  
  RESULTS
  S. pyogenes 237 displayed a KG insertion after position 69 in ribosomal protein L4. S. pyogenes 544 contained a C2611U mutation in domain V of 23S rRNA.
  
  
  CONCLUSIONS
  Mutations at a similar position in ribosomal protein L4 and 23S rRNA have been reported previously in macrolide-resistant pneumococci. This report shows that similar mutations can be found in macrolide-resistant S. pyogenes.
authors.affiliation: Service de Microbiologie, Hôpital Côte de Nacre, UFR de Médecine, Av. Côte de Nacre, 14033 Caen, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malbruny
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nagai
authors.forename: Maëlle
authors.initials: M
authors.lastname: Coquemont
authors.forename: Bülent
authors.initials: B
authors.lastname: Bozdogan
authors.forename: Arjana Tambic
authors.initials: AT
authors.lastname: Andrasevic
authors.forename: Helena
authors.initials: H
authors.lastname: Hupkova
authors.forename: Roland
authors.initials: R
authors.lastname: Leclercq
authors.forename: Peter C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007223:Infant; D018942:Macrolides; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000706:statistics & numerical data; D009154:Mutation / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D012269:Ribosomal Proteins