Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
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DOI：
10.1038/s41467-020-17327-w
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发表时间：
2020-07-10
影响因子：
16.6
通讯作者：
Kwambana-Adams, Brenda A.
中科院分区：
文献类型：
--
作者：
Chaguza, Chrispin;Senghore, Madikay;Kwambana-Adams, Brenda A.
肺炎链球菌（一种适应人类的机会性病原体）的基因组进化、传播和发病机制主要由鼻咽携带驱动。然而，人们对自然定植过程中基因组的变化知之甚少。在这里，我们使用全基因组测序来研究 98 名婴儿中自然携带的肺炎球菌的宿主内微进化，这些婴儿从出生到 12 个月在高携带非洲环境中连续进行密集采样。我们发现，在肺炎链球菌和其他细菌中，中性进化和核苷酸取代率比在较长时间尺度上观察到的速度快了四十倍，从而驱动了宿主内肺炎球菌的高度遗传多样性。通过实时宿主内同源重组，在定植过程中出现高度分化的共存菌株变体，而其余菌株则在多个定植过程中共同传播或独立获得。基因和基因间的平行进化尤其发生在抗生素抗性、免疫逃避和上皮粘附基因中。我们的研究结果表明，在自然定植过程中，宿主内的微进化是快速且适应性强的。肺炎链球菌是一种机会性病原体，无症状定植是侵袭性疾病的前兆。在这里，作者展示了九十八名婴儿中自然获得的肺炎球菌在高核苷酸取代率和宿主内同源重组的驱动下在宿主内快速进化。
Genomic evolution, transmission and pathogenesis of Streptococcus pneumoniae, an opportunistic human-adapted pathogen, is driven principally by nasopharyngeal carriage. However, little is known about genomic changes during natural colonisation. Here, we use whole-genome sequencing to investigate within-host microevolution of naturally carried pneumococci in ninety-eight infants intensively sampled sequentially from birth until twelve months in a high-carriage African setting. We show that neutral evolution and nucleotide substitution rates up to forty-fold faster than observed over longer timescales in S. pneumoniae and other bacteria drives high within-host pneumococcal genetic diversity. Highly divergent co-existing strain variants emerge during colonisation episodes through real-time intra-host homologous recombination while the rest are co-transmitted or acquired independently during multiple colonisation episodes. Genic and intergenic parallel evolution occur particularly in antibiotic resistance, immune evasion and epithelial adhesion genes. Our findings suggest that within-host microevolution is rapid and adaptive during natural colonisation.Streptococcus pneumoniae is an opportunistic pathogen and asymptomatic colonization is a precursor for invasive disease. Here the authors show rapid within-host evolution of naturally acquired pneumococci in ninety-eight infants driven by high nucleotide substitution rates and intra-host homologous recombination.