Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Darwin College, University of Cambridge, Silver Street, Cambridge, UK.
Nat Commun. 2020 Jul 10;11(1):3442. doi: 10.1038/s41467-020-17327-w.
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.
肺炎链球菌是一种机会性人类病原体，其基因组进化、传播和发病机制主要由鼻咽携带驱动。然而，对于自然定植过程中的基因组变化知之甚少。在这里，我们使用全基因组测序来研究 98 名婴儿在高携带的非洲环境中从出生到 12 个月期间连续进行的、自然携带的肺炎链球菌在宿主内的微进化。我们表明，中性进化和核苷酸替换率比在更长时间内观察到的肺炎链球菌和其他细菌的替换率快四十倍，这导致了宿主内肺炎链球菌遗传多样性的增加。在定植过程中，通过实时的宿主内同源重组，出现了高度分化的共存菌株变体，而其余的则在多次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特别发生在抗生素耐药性、免疫逃避和上皮黏附基因中。我们的研究结果表明，自然定植过程中，宿主内微进化是快速和适应性的。
