title: Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.
abstract: We investigated the correlation between the genetic variation within mef(A)-msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive strains were selected according to erythromycin MIC (4-32 μg/mL), and their mef(A)-msr(D) regions were sequenced. Strains were classified according to the bacteriophage carrying mef(A)-msr(D). A new Φm46.1 genetic variant was found in 8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus that could have shaped the apparent mosaic structure of the region. There was a general correlation between mef(A)-msr(D) sequence and erythromycin resistance level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)-carrying Φm46.1 indicated that key determinants may not all reside within the mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes in the level of antibiotic resistance in S. pyogenes.
authors.affiliation: School of Pharmacy, University of Camerino, Camerino, Italy. Electronic address: luca.vitali@unicam.it.
authors.forename: Luca Agostino
authors.initials: LA
authors.lastname: Vitali
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Di Luca
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Prenna
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
authors.forename: Dezemona
authors.initials: D
authors.lastname: Petrelli
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology*; D022761:Gene Transfer, Horizontal; D056426:Genetic Loci; D014644:Genetic Variation; D006801:Humans; D008242:Lysogeny; D026901:Membrane Transport Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D039002:Prophages / Q000235:genetics; D017422:Sequence Analysis, DNA; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000821:virology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D026901:Membrane Transport Proteins; D004917:Erythromycin
keywords: Antimicrobial resistance; Efflux; Group A streptococcus; Macrolide