Mostowy Rafal J, Croucher Nicholas J, De Maio Nicola, Chewapreecha Claire, Salter Susannah J, Turner Paul, Aanensen David M, Bentley Stephen D, Didelot Xavier, Fraser Christophe
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Mol Biol Evol. 2017 Oct 1;34(10):2537-2554. doi: 10.1093/molbev/msx173.
Diversity of the polysaccharide capsule in Streptococcus pneumoniae-main surface antigen and the target of the currently used pneumococcal vaccines-constitutes a major obstacle in eliminating pneumococcal disease. Such diversity is genetically encoded by almost 100 variants of the capsule biosynthesis locus, cps. However, the evolutionary dynamics of the capsule remains not fully understood. Here, using genetic data from 4,519 bacterial isolates, we found cps to be an evolutionary hotspot with elevated substitution and recombination rates. These rates were a consequence of relaxed purifying selection and positive, diversifying selection acting at this locus, supporting the hypothesis that the capsule has an increased potential to generate novel diversity compared with the rest of the genome. Diversifying selection was particularly evident in the region of wzd/wze genes, which are known to regulate capsule expression and hence the bacterium's ability to cause disease. Using a novel, capsule-centered approach, we analyzed the evolutionary history of 12 major serogroups. Such analysis revealed their complex diversification scenarios, which were principally driven by recombination with other serogroups and other streptococci. Patterns of recombinational exchanges between serogroups could not be explained by serotype frequency alone, thus pointing to nonrandom associations between co-colonizing serotypes. Finally, we discovered a previously unobserved mosaic serotype 39X, which was confirmed to carry a viable and structurally novel capsule. Adding to previous discoveries of other mosaic capsules in densely sampled collections, these results emphasize the strong adaptive potential of the bacterium by its ability to generate novel antigenic diversity by recombination.
肺炎链球菌中多糖荚膜的多样性——主要表面抗原及当前所用肺炎球菌疫苗的靶点——是消除肺炎球菌疾病的主要障碍。这种多样性由荚膜生物合成位点（cps）的近100个变体进行基因编码。然而，荚膜的进化动态仍未被完全理解。在此，我们利用来自4519株细菌分离株的基因数据，发现cps是一个进化热点，其替换率和重组率均有所升高。这些速率是纯化选择放松以及该位点存在正向、多样化选择的结果，支持了与基因组其他部分相比，荚膜产生新多样性的潜力更大这一假说。多样化选择在wzd/wze基因区域尤为明显，已知该区域调控荚膜表达，进而影响细菌致病能力。我们采用一种以荚膜为中心的全新方法，分析了12个主要血清群的进化史。此类分析揭示了它们复杂的多样化情形，主要由与其他血清群及其他链球菌的重组所驱动。血清群之间的重组交换模式不能仅由血清型频率来解释，这表明共同定植血清型之间存在非随机关联。最后，我们发现了一种先前未观察到的嵌合血清型39X，经证实其携带一种具有活性且结构新颖的荚膜。这些结果连同之前在密集采样集合中对其他嵌合荚膜的发现，强调了该细菌通过重组产生新抗原多样性的能力所具有的强大适应潜力。
