Selective and genetic constraints on pneumococcal serotype switching.
Selective and genetic constraints on pneumococcal serotype switching.
复制标题
DOI：
10.1371/journal.pgen.1005095
复制
发表时间：
2015-03
期刊：
影响因子：
4.5
通讯作者：
Hanage WP
中科院分区：
文献类型：
--
作者：
Croucher NJ;Kagedan L;Thompson CM;Parkhill J;Bentley SD;Finkelstein JA;Lipsitch M;Hanage WP
肺炎链球菌分离株通常表达90多种免疫可区分的多糖胶囊（血清型）中的一种，可根据与某些抗体的交叉反应性将其分为“血清群”。肺炎球菌可以通过影响荚膜多糖合成位点的重组来改变其血清型。使用来自肺炎球菌携带系统调查的616个全基因组序列，对20个这样的“血清型转换”事件进行了充分表征。其中11个是血清组内开关，根据观察到的血清型分布，表示高度显著（p < 0.0001）富集。虽然导致血清组间开关的重组都跨越了整个cps位点，但一些导致血清组内开关的重组却没有。然而，较高的血清组内转换率既不能用更频繁、更短的重组来完全解释，也不能用与β -内酰胺抗性相关的基因的遗传联系来完全解释。这表明观察到的模式是选择保存血清组的结果。对在共同遗传背景下表达不同血清型的菌株进行表型分析，以检验基因型是否在生理上适应于特定的血清型。这些数据与cps位点与基因组其余部分之间的上位性相互作用是一致的，这些相互作用是特定于血清型的，而不是血清组，这意味着它们不太可能解释所观察到的囊型分布。排除这些遗传和生理假说表明，未来的工作应侧重于其他机制，如宿主免疫在同一血清群中跨越多种血清型，这可能解释观察到的模式。肺炎链球菌是一种主要的呼吸道病原体，在世界范围内造成了很高的发病率和死亡率。目前的抗肺炎球菌疫苗针对细菌的多糖胶囊，其中至少有95种不同的变体（“血清型”）是已知的，它们被分为“血清群”。细菌可以通过被称为“转换”的基因重组来改变它们的血清型，这可以使菌株逃避疫苗诱导的免疫。通过将流行病学数据与全基因组测序相结合，这项工作在引入常规抗肺炎球菌疫苗接种后收集的细菌样本中发现了一种强大且意想不到的血清型转换模式：在同一血清群中，一种血清型转换为另一种血清型的可能性比偶然预期的要大得多。提出并检验了几种假说来解释这种模式，包括基因重组的局限性，决定血清型的基因与基因组其余部分之间的相互作用，以及细菌代谢施加的限制。这提供了关于肺炎链球菌进化的新信息，特别是关于随着新疫苗的引入，细菌可能如何多样化。
Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes), which can be classified into “serogroups” based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps) locus. Twenty such “serotype switching” events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001) enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β–lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern. Streptococcus pneumoniae is a major respiratory pathogen responsible for a high burden of morbidity and mortality worldwide. Current anti-pneumococcal vaccines target the bacterium’s polysaccharide capsule, of which at least 95 different variants (‘serotypes’) are known, which are classified into ‘serogroups’. Bacteria can change their serotype through genetic recombination, termed ‘switching’, which can allow strains to evade vaccine-induced immunity. By combining epidemiological data with whole genome sequencing, this work finds a robust and unexpected pattern of serotype switching in a sample of bacteria collected following the introduction of routine anti-pneumococcal vaccination: switching was much more likely to exchange one serotype for another within the same serogroup than expected by chance. Several hypotheses are presented and tested to explain this pattern, including limitations of genetic recombination, interactions between the genes that determine serotype and the rest of the genome, and the constraints imposed by bacterial metabolism. This provides novel information on the evolution of S. pneumoniae, particularly regarding how the bacterium might diversify as newer vaccines are introduced.
登录
查看更多内容
影响因子：
3.6
作者：
Black, S;Shinefield, H;Edwards, K
通讯作者：
Edwards, K
影响因子：
6.7
作者：
Johnston C;Martin B;Granadel C;Polard P;Claverys JP
通讯作者：
Claverys JP
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：
6.7
作者：
Croucher, Nicholas J.;Harris, Simon R.;Bentley, Stephen D.
通讯作者：
Bentley, Stephen D.
影响因子：
3.3
作者：
Croucher NJ;Chewapreecha C;Hanage WP;Harris SR;McGee L;van der Linden M;Song JH;Ko KS;de Lencastre H;Turner C;Yang F;Sá-Leão R;Beall B;Klugman KP;Parkhill J;Turner P;Bentley SD
通讯作者：
Bentley SD