Pneumococcal Capsule Synthesis Locus cps as Evolutionary Hotspot with Potential to Generate Novel Serotypes by Recombination.
Pneumococcal Capsule Synthesis Locus cps as Evolutionary Hotspot with Potential to Generate Novel Serotypes by Recombination.
复制标题
DOI：
10.1093/molbev/msx173
复制
发表时间：
2017-10-01
影响因子：
10.7
通讯作者：
Fraser C
中科院分区：
文献类型：
--
作者：
Mostowy RJ;Croucher NJ;De Maio N;Chewapreecha C;Salter SJ;Turner P;Aanensen DM;Bentley SD;Didelot X;Fraser C
肺炎链球菌的主要表面抗原和目前使用的肺炎球菌疫苗的靶标--肺炎链球菌的多糖壳的多样性构成了消除肺炎球菌疾病的主要障碍。这种多样性是由近100个囊膜生物合成位点cps的变异基因编码的。然而，对太空舱的进化动力学仍未完全了解。在这里，使用4519个细菌分离株的遗传数据，我们发现cps是一个具有更高的替代和重组率的进化热点。这些比率是宽松的纯化选择和作用于该基因座的正向、多样化选择的结果，支持了这样的假设，即与基因组的其余部分相比，被膜具有更大的潜力产生新的多样性。多样化的选择在wzd/wze基因区域尤为明显，众所周知，wzd/wze基因可以调节衣壳的表达，从而调节细菌的致病能力。使用一种新颖的、以胶囊为中心的方法，我们分析了12个主要血清群的进化史。这种分析揭示了它们复杂的多样化情况，这主要是由与其他血清群和其他链球菌的重组推动的。血清组之间的重组交换模式不能仅用血清型频率来解释，因此表明共同定植的血清型之间存在非随机关联。最后，我们发现了一种以前没有观察到的马赛克血清型39X，它被证实携带有一种可行的、结构新颖的胶囊。加上之前在密集采样样本中发现的其他马赛克胶囊，这些结果强调了该细菌通过重组产生新的抗原多样性的能力所具有的强大的适应潜力。
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.
登录
查看更多内容
影响因子：
3.2
作者：
Aanensen, David M.;Mavroldi, Angeliki;Spratt, Brian G.
通讯作者：
Spratt, Brian G.
DOI：
10.1093/bioinformatics/btp347
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Assefa S;Keane TM;Otto TD;Newbold C;Berriman M
通讯作者：
Berriman M
影响因子：
5.4
作者：
Croucher NJ;Hanage WP;Harris SR;McGee L;van der Linden M;de Lencastre H;Sá-Leão R;Song JH;Ko KS;Beall B;Klugman KP;Parkhill J;Tomasz A;Kristinsson KG;Bentley SD
通讯作者：
Bentley SD
影响因子：
4.5
作者：
Croucher NJ;Kagedan L;Thompson CM;Parkhill J;Bentley SD;Finkelstein JA;Lipsitch M;Hanage WP
通讯作者：
Hanage WP
影响因子：
3.1
作者：
BRILES, DE;CRAIN, MJ;YOTHER, J
通讯作者：
YOTHER, J