Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
mBio. 2020 May 19;11(3):e00937-20. doi: 10.1128/mBio.00937-20.
(pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus () genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D has three large regions syntenic to and highly homologous with loci from serotype 6C, serotype 39, and an oral streptococcus strain ( SK145). The 10D region syntenic to SK145 is about 6 kb and has a short gene fragment of α at the 5' end. The presence of this nonfunctional α fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination. The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.
（肺炎球菌）是一种产生结构多样荚膜多糖的主要人类病原体。广泛使用针对肺炎球菌荚膜的高度成功的肺炎球菌结合疫苗（PCV）大大减少了疫苗类型的感染，但增加了非疫苗血清型的感染。在此，我们通过确定其独特的化学结构和所有荚膜合成基因座（）基因的生物合成作用，报告了一种新的第 100 种荚膜类型，命名为血清型 10D。10D 的名称反映了其与血清型 10A 的血清学交叉反应，以及在 23 价肺炎球菌疫苗中免疫接种 10A 多糖时出现的交叉调理抗体。遗传分析表明，10D 具有三个与血清型 6C、血清型 39 和口腔链球菌菌株（SK145）的 基因座高度同源的大片段。与 SK145 同源的 10D 区域约为 6kb，在 5'端具有一个短的α基因片段。这个无功能的α片段的存在为最近从口腔链球菌到肺炎球菌的种间遗传转移提供了有力的证据。由于口腔链球菌具有大量的 基因座，广泛使用 PCV 可能会通过种间重组导致新型血清型的出现。荚膜多糖对肺炎球菌的致病性至关重要，每年全球有数百万人因此死亡。目前可用的肺炎球菌疫苗旨在诱导针对引起疾病的肺炎球菌分离株荚膜多糖的抗体，并且这些抗体仅提供针对表达疫苗靶向荚膜的肺炎球菌的保护。由于肺炎球菌可以产生不同的荚膜多糖，从而降低疫苗的有效性，因此跟踪新型肺炎球菌荚膜类型的出现以及这些新的荚膜是如何产生的非常重要。在此，我们描述了一种具有独特化学和血清学特性的新型第 100 种肺炎球菌荚膜类型。该荚膜类型因其与 10A 的血清学相似性而被命名为 10D。遗传研究提供了强有力的证据，证明肺炎球菌通过捕获来自口腔链球菌的大片段遗传片段产生了 10D 荚膜多糖。这种种间遗传交换可以极大地增加肺炎球菌荚膜的多样性，并使血清型转变复杂化。
