title: Genome-wide dissection of globally emergent multi-drug resistant serotype 19A Streptococcus pneumoniae.
abstract: BACKGROUND
  Emergence of multi-drug resistant (MDR) serotype 19A Streptococcus pneumoniae (SPN) is well-documented but causal factors remain unclear. Canadian SPN isolates (1993-2008, n = 11,083) were serotyped and in vitro susceptibility tested. A subset of MDR 19A were multi-locus sequence typed (MLST) and representative isolates' whole genomes sequenced.
  
  
  RESULTS
  MDR 19A increased in the post-PCV7 era while 19F, 6B, and 23F concurrently declined. MLST of MDR 19A (n = 97) revealed that sequence type (ST) 320 predominated. ST320 was unique amongst MDR 19A in that its minimum inhibitory concentration (MIC) values for penicillin, amoxicillin, ceftriaxone, and erythromycin were higher than for other ST present amongst post-PCV7 MDR 19A. DNA sequencing revealed that alleles at key drug resistance loci pbp2a, pbp2x, pbp2b, ermB, mefA/E, and tetM were conserved between pre-PCV7 ST 320 19F and post-PCV7 ST 320 19A most likely due to a capsule switch recombination event. A genome wide comparison of MDR 19A ST320 with MDR 19F ST320 identified 822 unique SNPs in 19A, 61 of which were present in antimicrobial resistance genes and 100 in virulence factors.
  
  
  CONCLUSIONS
  Our results suggest a complex genetic picture where high-level drug resistance, vaccine selection pressure, and SPN mutational events have created a "perfect storm" for the emergence of MDR 19A.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada. dylan.pillai@oahpp.ca
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Pillai
authors.forename: Dea
authors.initials: D
authors.lastname: Shahinas
authors.forename: Alla
authors.initials: A
authors.lastname: Buzina
authors.forename: Remy A
authors.initials: RA
authors.lastname: Pollock
authors.forename: Rachel
authors.initials: R
authors.lastname: Lau
authors.forename: Krishna
authors.initials: K
authors.lastname: Khairnar
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Karen
authors.initials: K
authors.lastname: Green
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002170:Canada; D055028:Comparative Genomic Hybridization; D019295:Computational Biology; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D016680:Genome, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D008826:Microbial Sensitivity Tests; D022242:Pneumococcal Vaccines; D017422:Sequence Analysis, DNA; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines