Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape.

Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape.
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DOI:
10.1093/gbe/evu120
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发表时间:
2014-06-10
影响因子:
3.3
通讯作者:
Bentley SD
Bentley SD
中科院分区:
生物学2区
文献类型:
--
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

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多重耐药肺炎链球菌台湾19 F-14(或PMEN 14)克隆首次在19 F血清型中观察到,该血清型是七价多糖结合疫苗(PCV 7)的靶向。然而,具有19 A血清型的“疫苗逃逸”PMEN 14分离株成为PCV 7后疾病的日益重要的原因。全基因组测序被用来表征173个肺炎球菌的最新进化,或与PMEN 14相关。这表明PMEN 14是一个起源于20世纪80年代后期的单一谱系,与近亲获得多重耐药性平行。检测到的4个血清型转换为19 A的其中一个产生了序列型(ST)320分离株的代表,这些分离株在PCV 7后非常成功。第二个产生了ST 236 19 A基因型,由于通过引起血清型变化的相同重组改变了pbp 1a和pbp 2x序列,因此对β-内酰胺类抗生素的耐药性降低。第三,产生了镶嵌胶囊生物合成位点,导致血清型19 A ST 271菌株。在没有接种疫苗的情况下,在来自泰国Maela难民营的一组分离株中也观察到了全球收集中通过同源重组的快速多样化,该收集也允许通过纵向采样在运输中观察到变异。这表明,一些肺炎球菌基因型产生了一个足够广泛的长期变异池,导致“软”选择性扫描:在选择压力变化(如疫苗引入)时平行出现多个突变体。这些突变体之间随后的竞争使得这种现象在没有对个体谱系进行深入采样的情况下难以检测。
The multidrug-resistant Streptococcus pneumoniae Taiwan19F-14, or PMEN14, clone was first observed with a 19F serotype, which is targeted by the heptavalent polysaccharide conjugate vaccine (PCV7). However, “vaccine escape” PMEN14 isolates with a 19A serotype became an increasingly important cause of disease post-PCV7. Whole genome sequencing was used to characterize the recent evolution of 173 pneumococci of, or related to, PMEN14. This suggested that PMEN14 is a single lineage that originated in the late 1980s in parallel with the acquisition of multiple resistances by close relatives. One of the four detected serotype switches to 19A generated representatives of the sequence type (ST) 320 isolates that have been highly successful post-PCV7. A second produced an ST236 19A genotype with reduced resistance to β-lactams owing to alteration of pbp1a and pbp2x sequences through the same recombination that caused the change in serotype. A third, which generated a mosaic capsule biosynthesis locus, resulted in serotype 19A ST271 isolates. The rapid diversification through homologous recombination seen in the global collection was similarly observed in the absence of vaccination in a set of isolates from the Maela refugee camp in Thailand, a collection that also allowed variation to be observed within carriage through longitudinal sampling. This suggests that some pneumococcal genotypes generate a pool of standing variation that is sufficiently extensive to result in “soft” selective sweeps: The emergence of multiple mutants in parallel upon a change in selection pressure, such as vaccine introduction. The subsequent competition between these mutants makes this phenomenon difficult to detect without deep sampling of individual lineages.
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