Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila
Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila
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DOI：
10.1038/s41564-019-0663-7
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发表时间：
2020-01-27
影响因子：
28.3
通讯作者：
O'Connor, Tamara J.
中科院分区：
文献类型：
--
作者：
Park, Jason M.;Ghosh, Soma;O'Connor, Tamara J.
毒力机制通常通过病原体与其宿主的持续相互作用而进化。相比之下，人们对环境中获得的病原体如何能够在不与人类相互作用的情况下引起疾病知之甚少。在这里，我们提供了实验证据的模型，军团菌在人类的发病机制，结果从环境中的多个阿米巴宿主的累积选择压力。使用转座子测序，我们确定嗜肺军团菌生长所需的基因在四个不同的阿米巴，定义通用的毒力因子通常需要在所有的宿主细胞类型和阿米巴特异性的辅助基因，确定主机范围。通过比较阿米巴和巨噬细胞中促进生长的基因，我们发现L。嗜肺细菌对每种阿米巴的感染导致不同毒力基因的积累，这些毒力基因共同允许在巨噬细胞中复制，并且在某些情况下导致这种宿主细胞类型的冗余。相反，一些细菌蛋白，促进复制阿米巴限制生长的巨噬细胞。因此，阿米巴强加的选择是一把双刃剑，对疾病既有积极的影响，也有消极的影响。比较多个军团菌属物种的基因组组成和宿主范围，我们表明，他们在环境中不同的进化轨迹导致了趋同进化的补偿毒力mechanism.This研究报告转座子测序分析，以确定嗜肺军团菌阿米巴宿主生存所需的基因，显示独特的基因集所需的毒力在不同的阿米巴。这使得毒力基因的积累，共同允许在巨噬细胞中复制，并在某些情况下，导致这种宿主细胞类型的冗余。
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.This study reports transposon sequencing analyses to identify genes required for Legionella pneumophila survival in amoeba hosts, showing that unique sets of genes are required for virulence in different amoebae. This enables the accumulation of virulence genes that collectively allow replication in macrophages and, in some cases, lead to redundancy in this host cell type.