Genome-wide dissection of globally emergent multi-drug resistant serotype 19A Streptococcus pneumoniae

• Published in: BMC genomics 2009-12, Vol.10 (1), p.642-642
• Main Authors: Pillai, Dylan R, Shahinas, Dea, Buzina, Alla, Pollock, Remy A, Lau, Rachel, Khairnar, Krishna, Wong, Andrew, Farrell, David J, Green, Karen, McGeer, Allison, Low, Donald E
• Format: Article
• Language: English
• Subjects: Amoxicillin; Anti-Bacterial Agents - pharmacology; Canada; Ceftriaxone; Colleges & universities; Comparative Genomic Hybridization; Computational Biology; Deoxyribonucleic acid; DNA; DNA sequencing; DNA, Bacterial - genetics; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Erythromycin; Gene expression; Gene mutations; Genetic aspects; Genetics; Genome, Bacterial; Genomes; Health aspects; Heptavalent Pneumococcal Conjugate Vaccine; Microbial Sensitivity Tests; Minimum inhibitory concentration; Multidrug resistance; Ontology; Penicillin; Pneumococcal Vaccines; Pneumonia; Polymerase chain reaction; Recombination; Research article; Sequence Analysis, DNA; Serotypes; Serotyping; Single-nucleotide polymorphism; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - classification; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - genetics; Vaccines; virulence factors
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-10-642

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. 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. 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.