全基因组剖析全球新兴的多药耐药血清型 19A 肺炎链球菌。

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.

背景

耐多药（MDR）血清型 19A 肺炎链球菌（SPN）的出现已有充分记录，但因果因素仍不清楚。对加拿大 SPN 分离株（1993-2008 年，n=11083）进行血清分型和体外药敏试验。对 MDR 19A 的一部分进行多位点序列分型（MLST），并对代表性分离株的全基因组进行测序。

结果

MDR 19A 在 PCV7 后时代增加，而 19F、6B 和 23F 则同时下降。MDR 19A 的 MLST（n=97）显示，主要序列型（ST）为 320。ST320 在 MDR 19A 中是独一无二的，因为其青霉素、阿莫西林、头孢曲松和红霉素的最低抑菌浓度（MIC）值高于 PCV7 后 MDR 19A 中其他 ST 的 MIC 值。DNA 测序显示，关键耐药基因位点 pbp2a、pbp2x、pbp2b、ermB、mefA/E 和 tetM 的等位基因在 PCV7 前 ST320 19F 和 PCV7 后 ST320 19A 之间是保守的，这很可能是由于荚膜转换重组事件。对 MDR 19A ST320 与 MDR 19F ST320 的全基因组比较发现，19A 中有 822 个独特的 SNP，其中 61 个存在于抗菌药物耐药基因中，100 个存在于毒力因子中。