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Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila
Nature Microbiology ( IF 20.5 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41564-019-0663-7
Jason M Park 1, 2 , Soma Ghosh 1 , Tamara J O'Connor 1
Affiliation  

Virulence mechanisms typically evolve through the continual interaction of a pathogen with its host. In contrast, it is poorly understood how environmentally acquired pathogens are able to cause disease without prior interaction with humans. Here, we provide experimental evidence for the model that Legionella pathogenesis in humans results from the cumulative selective pressures of multiple amoebal hosts in the environment. Using transposon sequencing, we identify Legionella pneumophila genes required for growth in four diverse amoebae, defining universal virulence factors commonly required in all host cell types and amoeba-specific auxiliary genes that determine host range. By comparing genes that promote growth in amoebae and macrophages, we show that adaptation of L. pneumophila to each amoeba causes the accumulation of distinct virulence genes that collectively allow replication in macrophages and, in some cases, leads to redundancy in this host cell type. In contrast, some bacterial proteins that promote replication in amoebae restrict growth in macrophages. Thus, amoebae-imposed selection is a double-edged sword, having both positive and negative impacts on disease. Comparing the genome composition and host range of multiple Legionella species, we demonstrate that their distinct evolutionary trajectories in the environment have led to the convergent evolution of compensatory virulence mechanisms.



中文翻译:

变形虫宿主的组合选择推动了人类病原体嗜肺军团菌的进化

毒力机制通常通过病原体与其宿主的持续相互作用而演变。相比之下,人们对环境获得的病原体如何能够在没有事先与人类相互作用的情况下引起疾病知之甚少。在这里,我们为人类军团病发病机制的模型提供了实验证据,该模型是由环境中多个变形虫宿主的累积选择压力引起的。使用转座子测序,我们确定了四种不同变形虫生长所需的嗜肺军团菌基因,定义了所有宿主细胞类型通常需要的通用毒力因子和确定宿主范围的变形虫特异性辅助基因通过比较促进变形虫和巨噬细胞生长的基因,我们表明适应每个变形虫的嗜肺军团菌都会导致不同毒力基因的积累,这些基因共同允许在巨噬细胞中进行复制,并且在某些情况下,会导致这种宿主细胞类型的冗余。相反,一些促进变形虫复制的细菌蛋白质会限制巨噬细胞的生长。因此,变形虫强加的选择是一把双刃剑,对疾病既有积极影响,也有消极影响。通过比较多种军团菌的基因组组成和宿主范围,我们证明了它们在环境中不同的进化轨迹导致了补偿性毒力机制的趋同进化。

更新日期:2020-01-27
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