High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains

J Infect Dis. 2003 Jun 1;187(11):1709-16. doi: 10.1086/374937. Epub 2003 May 15.


Incidence of resistance to erythromycin at our institution reached 53% in 122 Staphylococcus aureus isolates obtained from patients with cystic fibrosis (CF) from 1997 to 1999. Macrolide-resistance genes were sought for in 20 erythromycin-resistant isolates from 9 patients with CF by use of polymerase chain reaction; 13 strains did not contain any known macrolide-resistance genes. Sequence of ribosomal genes rrl (23S rRNA), rplD (L4 protein), and rplV (L22 protein) revealed the presence of mutations in the target site of macrolides in 15 of the 20 isolates. A higher proportion of hypermutator strains was observed in a group of 89 CF staphylococcal isolates, compared with that in the 74 non-CF control isolates (13/89 vs. 1/74 with resistance to rifampin [P=.0045]; 9/89 vs. 1/74 with resistance to streptomycin [P=.04]). Various mutations or deletions of the mutator mutS gene were found not only in 5 of 11 hypermutable strains but also in 3 nonhypermutable strains harboring a large number of ribosomal mutations. The presence of a high proportion of hypermutable strains might explain the adaptation of certain strains in the patients, as well as the emergence of macrolide resistance as a result of antibiotic selective pressure in CF.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins*
  • Cystic Fibrosis / microbiology*
  • DNA, Ribosomal / genetics
  • DNA-Binding Proteins*
  • Drug Resistance, Multiple, Bacterial*
  • Escherichia coli Proteins / genetics
  • Female
  • Humans
  • Macrolides
  • Male
  • MutS DNA Mismatch-Binding Protein
  • Mutation / genetics*
  • Phenotype
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Macrolides
  • Adenosine Triphosphatases
  • MutS DNA Mismatch-Binding Protein
  • MutS protein, E coli