Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation.
Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation.
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DOI：
10.1093/molbev/msv160
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发表时间：
2015-11
影响因子：
10.7
通讯作者：
Schulenburg H
中科院分区：
文献类型：
--
作者：
Jansen G;Crummenerl LL;Gilbert F;Mohr T;Pfefferkorn R;Thänert R;Rosenstiel P;Schulenburg H
共生相互作用对于后生动物的功能是不可或缺的，但它们的起源和进化仍然难以捉摸。我们使用受控进化实验来证明铜绿假单胞菌（一种最初的致病细菌）和后生动物宿主秀丽隐杆线虫之间出现了新型共生相互作用。我们证明，共生主义是通过毒力丧失而进化的，因为它为细菌提供了双重适应性优势：宿主内适应性增强和感染更大的宿主群体。共生现象的产生与宿主免疫状态无关，因为免疫受损的秀丽隐杆线虫敲除的适应性路径与野生型没有不同。对 125 个细菌种群基因组适应的时间动态的剖析揭示了独立生物复制中早期共生主义的高度平行进化。适应主要是通过进化早期出现的全局调节因子 lasR 中的移码突变和聚合酶基因 rpoB 中的非同义点突变来实现。 lasR 的基因敲除不仅证实了其在毒力减弱中的作用，而且表明进一步的突变对于完全共生表型是必要的。正如我们在这里观察到的，从致病性到共生性的进化转变是由 lasR 等全局调节因子的突变促进的，因为很少有遗传变化会导致整个基因组的多效性效应，并具有很大的表型效应。最后，我们发现，在适应免疫功能低下的宿主的细菌中，核苷酸多样性比在适应免疫功能正常的宿主的细菌中增加得更快。尽管如此，不同宿主类型的进化结果是具有可比性的。因此，共生现象可以独立于宿主免疫状态而进化，仅作为细菌适应新宿主的副作用。
Symbiotic interactions are indispensable for metazoan function, but their origin and evolution remain elusive. We use a controlled evolution experiment to demonstrate the emergence of novel commensal interactions between Pseudomonas aeruginosa, an initially pathogenic bacterium, and a metazoan host, Caenorhabditis elegans. We show that commensalism evolves through loss of virulence, because it provides bacteria with a double fitness advantage: Increased within-host fitness and a larger host population to infect. Commensalism arises irrespective of host immune status, as the adaptive path in immunocompromised C. elegans knockouts does not differ from that in wild type. Dissection of temporal dynamics of genomic adaptation for 125 bacterial populations reveals highly parallel evolution of incipient commensalism across independent biological replicates. Adaptation is mainly achieved through frame shift mutations in the global regulator lasR and nonsynonymous point mutations in the polymerase gene rpoB that arise early in evolution. Genetic knockouts of lasR not only corroborate its role in virulence attenuation but also show that further mutations are necessary for the fully commensal phenotype. The evolutionary transition from pathogenicity to commensalism as we observe here is facilitated by mutations in global regulators such as lasR, because few genetic changes cause pleiotropic effects across the genome with large phenotypic effects. Finally, we found that nucleotide diversity increased more quickly in bacteria adapting to immunocompromised hosts than in those adapting to immunocompetent hosts. Nevertheless, the outcome of evolution was comparable across host types. Commensalism can thus evolve independently of host immune state solely as a side-effect of bacterial adaptation to novel hosts.