Structure and Distribution of an Unusual Chimeric Genetic Element Encoding Macrolide Resistance in Phylogenetically Diverse Clones of Group A Streptococcus

J Infect Dis. 2003 Dec 15;188(12):1898-908. doi: 10.1086/379897. Epub 2003 Dec 9.

Abstract

The resistance of group A Streptococcus (GAS) to macrolide antibiotics is now a worldwide problem. Preliminary sequencing of the genome of an erythromycin-resistant serotype M6 clone that was responsible for a pharyngitis outbreak in Pittsburgh, Pennsylvania, was conducted to determine the structure of the genetic element containing the mefA gene, which encodes a macrolide efflux protein. The mefA gene is associated with a 58.8-kb chimeric genetic element composed of a transposon inserted into a prophage. This element also encodes a putative extracellular protein with a cell-wall anchoring motif (LPKTG) located at the carboxyterminus. The mefA element was present in phylogenetically diverse GAS strains isolated throughout the United States. Culture supernatants, prepared after mitomycin C treatment, of a strain representing the outbreak clone contained mefA element DNA in a DNAse-resistant form. Together, these data provide new information about the molecular genetic basis of macrolide resistance and dissemination in GAS strains.

MeSH terms

  • Amino Acid Motifs
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacteriophages / drug effects
  • Bacteriophages / ultrastructure
  • Chromosome Mapping
  • Clone Cells
  • DNA Transposable Elements
  • Drug Resistance, Bacterial
  • Drug Resistance, Microbial
  • Genetic Variation
  • Genome, Viral*
  • Humans
  • Macrolides / pharmacology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Mitomycin / pharmacology
  • Molecular Weight
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Open Reading Frames
  • Prophages / genetics
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / genetics*
  • Streptococcus pyogenes / virology
  • United States

Substances

  • Bacterial Proteins
  • DNA Transposable Elements
  • Macrolides
  • MefA protein, Streptococcus
  • Membrane Proteins
  • Nucleic Acid Synthesis Inhibitors
  • Mitomycin