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

Pillai DR, Shahinas D, Buzina A, Pollock RA, Lau R, Khairnar K, Wong A, Farrell DJ, Green K, McGeer A, Low DE - BMC Genomics (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada. dylan.pillai@oahpp.ca

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.

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Serotype trends amongst multi-drug resistant (MDR) strains obtained from the Canadian Bacterial Surveillance Network between 1993 and 2008 (n = 11,083). MDR 19F (n = 477), 23F (n = 150), and 6B (n = 221) emerged in the pre- PCV 7 introduction era (before 2001) and continued to rise during vaccine introduction (2002-2005), then declined in post-PCV7 introduction era (2006 onwards). MDR 19A (n = 97) was present in the pre-PCV7 at very low levels and began to rise soon after PCV7 was introduced country-wide. Data for 1999 and 2000 were not collected. Data are presented as the percent of all MDR isolates collected for the given year.
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Figure 1: Serotype trends amongst multi-drug resistant (MDR) strains obtained from the Canadian Bacterial Surveillance Network between 1993 and 2008 (n = 11,083). MDR 19F (n = 477), 23F (n = 150), and 6B (n = 221) emerged in the pre- PCV 7 introduction era (before 2001) and continued to rise during vaccine introduction (2002-2005), then declined in post-PCV7 introduction era (2006 onwards). MDR 19A (n = 97) was present in the pre-PCV7 at very low levels and began to rise soon after PCV7 was introduced country-wide. Data for 1999 and 2000 were not collected. Data are presented as the percent of all MDR isolates collected for the given year.

Mentions: Serotypes and antibiotic susceptibility testing were determined for n = 11,083 isolates over a 15 year period. Serotype surveillance demonstrated a reduction in vaccine serotypes from the era immediately prior to PCV7 introduction in Canada (pre-PCV7, 1993-2001), PCV7 introduction era (2002-2005), and post-PCV7 introduction era (2006-present) (our unpublished data). We focus here on the MDR serotypes. Figure 1 graphically depicts the trends in MDR (defined as non-susceptibility to penicillin plus two other antibiotics) serotypes 6B, 23F, 19F and 19A, the major contributors to MDR SPN in this population as a percent of all MDR isolates collected for that year. While other serotypes contribute to MDR, their numbers were not significantly large in our database.


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

Pillai DR, Shahinas D, Buzina A, Pollock RA, Lau R, Khairnar K, Wong A, Farrell DJ, Green K, McGeer A, Low DE - BMC Genomics (2009)

Serotype trends amongst multi-drug resistant (MDR) strains obtained from the Canadian Bacterial Surveillance Network between 1993 and 2008 (n = 11,083). MDR 19F (n = 477), 23F (n = 150), and 6B (n = 221) emerged in the pre- PCV 7 introduction era (before 2001) and continued to rise during vaccine introduction (2002-2005), then declined in post-PCV7 introduction era (2006 onwards). MDR 19A (n = 97) was present in the pre-PCV7 at very low levels and began to rise soon after PCV7 was introduced country-wide. Data for 1999 and 2000 were not collected. Data are presented as the percent of all MDR isolates collected for the given year.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2807444&req=5

Figure 1: Serotype trends amongst multi-drug resistant (MDR) strains obtained from the Canadian Bacterial Surveillance Network between 1993 and 2008 (n = 11,083). MDR 19F (n = 477), 23F (n = 150), and 6B (n = 221) emerged in the pre- PCV 7 introduction era (before 2001) and continued to rise during vaccine introduction (2002-2005), then declined in post-PCV7 introduction era (2006 onwards). MDR 19A (n = 97) was present in the pre-PCV7 at very low levels and began to rise soon after PCV7 was introduced country-wide. Data for 1999 and 2000 were not collected. Data are presented as the percent of all MDR isolates collected for the given year.
Mentions: Serotypes and antibiotic susceptibility testing were determined for n = 11,083 isolates over a 15 year period. Serotype surveillance demonstrated a reduction in vaccine serotypes from the era immediately prior to PCV7 introduction in Canada (pre-PCV7, 1993-2001), PCV7 introduction era (2002-2005), and post-PCV7 introduction era (2006-present) (our unpublished data). We focus here on the MDR serotypes. Figure 1 graphically depicts the trends in MDR (defined as non-susceptibility to penicillin plus two other antibiotics) serotypes 6B, 23F, 19F and 19A, the major contributors to MDR SPN in this population as a percent of all MDR isolates collected for that year. While other serotypes contribute to MDR, their numbers were not significantly large in our database.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada. dylan.pillai@oahpp.ca

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.

Show MeSH
Related in: MedlinePlus