title: Mobile elements and chromosomal changes associated with MLS resistance phenotypes of invasive pneumococci recovered in the United States.
abstract: Pneumococcal macrolide resistance is usually expressed as one of two phenotypes: the M phenotype conferred by the mef gene or the MLSB phenotype caused by modification of ribosomal targets, most commonly mediated by an erm methylase. Target-site modification leading to antibiotic resistance can also occur due to sequence mutations within the 23S rRNA or the L4 and L22 riboproteins. We screened 4,535 invasive isolates resistant to erythromycin and 18 invasive isolates nonsusceptible to quinupristin-dalfopristin (Q-D) to deduce the potential mechanisms involved. Of 4,535 erythromycin-resistant isolates, 66.2% were polymerase chain reaction (PCR)-positive for mef alone, 17.8% for ermB alone, and 15.1% for both mef and ermB. Thirty-seven isolates (0.9%) were PCR negative for both determinants. Of these, 3 were positive for ermA (subclass ermTR) and 25 had chromosomal mutations. No chromosomal mutations (in 23S rRNA, rplD, or rplV) nor any of the macrolides/lincosamides/streptogramin (MLS) resistance genes screened for (ermT, ermA, cfr, lsaC, and vgaA) were found in the remaining nine isolates. Of 18 Q-D nonsusceptible isolates, 14 had chromosomal mutations and one carried both mef and ermB; no chromosomal mutations or other resistance genes were found in 3 isolates. Overall, we found 28 mutations, 13 of which have not been previously described in Streptococcus pneumoniae. The role of these mutations remains to be confirmed by transformation assays.
authors.affiliation: 1 Hubert Department of Global Health, Rollins School of Public Health, Emory University , Atlanta, Georgia .
authors.forename: Paulina A
authors.initials: PA
authors.lastname: Hawkins
authors.forename: Sopio
authors.initials: S
authors.lastname: Chochua
authors.forename: Delois
authors.initials: D
authors.lastname: Jackson
authors.forename: Bernard
authors.initials: B
authors.lastname: Beall
authors.forename: Lesley
authors.initials: L
authors.lastname: McGee
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002876:Chromosomes, Bacterial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D055231:Lincosamides / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D010641:Phenotype; D011008:Pneumococcal Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics*; D025361:Streptogramins / Q000494:pharmacology; D014481:United States; D014769:Virginiamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D055231:Lincosamides; D018942:Macrolides; D025361:Streptogramins; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D004917:Erythromycin