title: Structure and distribution of an unusual chimeric genetic element encoding macrolide resistance in phylogenetically diverse clones of group A Streptococcus.
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.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana 59840, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Banks
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: Kent D
authors.initials: KD
authors.lastname: Barbian
authors.forename: Judith M
authors.initials: JM
authors.lastname: Martin
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001435:Bacteriophages / Q000187:drug effects / Q000648:ultrastructure; D002874:Chromosome Mapping; D002999:Clone Cells; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial; D004352:Drug Resistance, Microbial; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D016685:Mitomycin / Q000494:pharmacology; D008970:Molecular Weight; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016366:Open Reading Frames; D039002:Prophages / Q000235:genetics; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics* / Q000821:virology; D014481:United States
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin