Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Room 543 - 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Room 543 - 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada; Department of Clinical Microbiology, Health Sciences Centre, Diagnostic Services - Shared Health Manitoba, MS673 - 820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada.
Vaccine. 2021 Sep 15;39(39):5474-5483. doi: 10.1016/j.vaccine.2021.08.061. Epub 2021 Aug 25.
The population of pneumococci circulating in Canada is constantly shifting under the pressures of antimicrobial and conjugate vaccine use. A new 15-valent pneumococcal conjugate vaccine (PCV), containing PCV-13 serotypes plus additional serotypes 22F and 33F, is currently undergoing clinical trials. The purpose of this study was to utilize whole genome sequencing to characterize invasive and respiratory Streptococcus pneumoniae isolates collected from Canadian hospitals pre- (2007-2011) and post-PCV-13 implementation (2012-2018) in Canada, particularly serotypes 22F and 33F. Isolates were obtained from the CANWARD 2007 to 2018 study. Overall, 597 S. pneumoniae isolates were sequenced using the Illumina MiSeq platform: 180 (101 respiratory, 79 blood) isolates of serotype 22F, 74 (41 respiratory, 33 blood) isolates of serotype 33F and 343 isolates randomly selected to broadly encompass pneumococci in Canada. Genomes were clustered using PopPUNK v2.0.2 and assigned to a Global Pneumococcal Sequencing Cluster (GPSC) and MLST sequence type (ST), and visualized using Cytoscape v3.8.0. Acquired resistance genes were identified using ResFinder 2.1, and genes with chromosomal mutations conferring resistance were extracted and compared to standard reference genome R6. PopPUNK clustering suggests that a clone of S. pneumoniae serotype 22F/ST433/GPSC19 demonstrating mefA-mediated macrolide resistance is emerging in Canada post-PCV-13 introduction, collected from both invasive and respiratory sources. Similarly, there is evidence to support a post-PCV-13 shift towards macrolide- and trimethoprim/sulfamethoxazole-resistant serotype 33F/ST100/GPSC3, including a cluster associated with invasive isolates. While some lineages containing vaccine serotypes were predominantly identified pre-PCV-13 implementation (serotype 5/GPSC8, serotype 7F/GPSC15), others (serotype 19A/GPSC1 and 4, serotype 3/GPSC12) continue to maintain a significant presence over time despite inclusion in PCV-13. Further genomic surveillance is necessary to determine additional trends over time in these upcoming vaccine serotypes, as well as the overall pneumococcal population in Canada.
在抗菌药物和结合疫苗使用的压力下，加拿大流行的肺炎球菌种群不断发生变化。一种新的 15 价肺炎球菌结合疫苗（PCV）目前正在进行临床试验，该疫苗包含 PCV-13 血清型以及另外的血清型 22F 和 33F。本研究的目的是利用全基因组测序技术，对加拿大医院在实施 PCV-13 前后（2007-2011 年和 2012-2018 年）收集的侵袭性和呼吸道肺炎链球菌分离株进行特征描述，特别是血清型 22F 和 33F。分离株来自 CANWARD 2007 至 2018 年的研究。总体而言，使用 Illumina MiSeq 平台对 597 株肺炎链球菌进行了测序：180 株（101 株呼吸道分离株，79 株血液分离株）血清型 22F 分离株，74 株（41 株呼吸道分离株，33 株血液分离株）血清型 33F 分离株，343 株随机选择的分离株广泛涵盖了加拿大的肺炎球菌。使用 PopPUNK v2.0.2 对基因组进行聚类，并将其分配到全球肺炎球菌测序聚类（GPSC）和 MLST 序列型（ST），并使用 Cytoscape v3.8.0 可视化。使用 ResFinder 2.1 识别获得的耐药基因，并提取与染色体突变相关的耐药基因，并与标准参考基因组 R6 进行比较。PopPUNK 聚类表明，在加拿大，一种携带 mefA 介导的大环内酯类耐药的血清型 22F/ST433/GPSC19 肺炎链球菌克隆在 PCV-13 引入后正在出现，从侵袭性和呼吸道来源都可以分离到该克隆。同样，有证据表明，在 PCV-13 引入后，血清型 33F/ST100/GPSC3 对大环内酯类和磺胺甲恶唑/甲氧苄啶的耐药性有所增加，包括与侵袭性分离株相关的一个聚类。虽然一些包含疫苗血清型的谱系主要在 PCV-13 实施之前被鉴定（血清型 5/GPSC8、血清型 7F/GPSC15），但其他谱系（血清型 19A/GPSC1 和 4、血清型 3/GPSC12）在 PCV-13 纳入后仍持续存在。需要进一步的基因组监测，以确定这些即将推出的疫苗血清型以及加拿大整体肺炎球菌种群随时间推移的其他趋势。
