Microbiology Department, Hospital Universitari de Bellvitge-Universitat de Barcelona-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
J Antimicrob Chemother. 2018 Nov 1;73(11):2941-2951. doi: 10.1093/jac/dky305.
To analyse the epidemiology and genetic evolution of PMEN3 (Spain9V-156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987-2016.
WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing.
Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b-ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of β-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background.
Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.
分析导致巴塞罗纳地区 1987-2016 年侵袭性肺炎球菌病（IPD）的青霉素不敏感肺炎链球菌 PMEN3（西班牙 9V-156）的流行病学和遗传进化。
对 46 个代表性分离株进行 WGS，并利用数据设计了其他分子分型方法，包括部分 MLST、PCR-RFLP 和表面暴露蛋白和原噬菌体的检测，以将剩余的分离株分配到谱系中。还对分离株进行了抗菌药物敏感性测试。
共鉴定出 227 例成人 PMEN3 引起的 IPD 病例。PENUM3 主要引起肺炎（84%），30 天死亡率为 23.1%。发现重组事件的证据，主要在三个区域，即荚膜操纵子（与荚膜转换有关）和包含 pbp2x 和 pbp1a、murM 基因和 pbp2b-ddl 区域的相邻区域。其中一些遗传变化产生了成功的新型变异血清型谱系，包括目前 PCV13 疫苗不包括的血清型 11A。其他遗传变化导致β-内酰胺类药物的 MIC 增加。值得注意的是，大多数分离株还携带编码 PblB 样蛋白的原噬菌体。尽管有这些适应，该克隆引起 IPD 的能力随着时间的推移仍然没有改变，突出了其核心遗传背景的重要性。
我们的研究表明，尽管广泛使用抗生素和结合疫苗，PENUM3 仍能成功适应并持续存在。除了增强对 PMEN3 分子进化的理解外，这些发现还强调了开发非血清型疫苗对抗肺炎球菌感染的必要性。
