Evolution of the Arsenal of Legionella pneumophila Effectors To Modulate Protist Hosts.
Evolution of the Arsenal of Legionella pneumophila Effectors To Modulate Protist Hosts.
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DOI：
10.1128/mbio.01313-18
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发表时间：
2018-10-09
期刊：
影响因子：
6.4
通讯作者：
Abu Kwaik Y
中科院分区：
文献类型：
--
作者：
Best A;Abu Kwaik Y
在人类宿主体内，嗜肺军团菌在肺泡巨噬细胞内复制，导致肺炎。然而，嗜肺乳杆菌是一种水生多能病原体，可在多种原生宿主内复制，包括阿米巴虫、过结肠虫和纤毛虫。在人类宿主体内，嗜肺军团菌在肺泡巨噬细胞内复制，导致肺炎。然而，嗜肺乳杆菌是一种水生多能病原体，可在多种原生宿主内复制，包括阿米巴虫、过结肠虫和纤毛虫。嗜肺乳杆菌的细胞内生活方式在两个进化上遥远的宿主巨噬细胞和原生生物是非常相似的。与众多原生宿主的共同进化塑造了嗜肺乳杆菌基因组的可塑性，其中包含许多通过跨界水平基因转移从原始真核宿主获得的基因编码的蛋白质。Dot/Icm型IVb易位系统将军团菌中的约6000种效应蛋白和嗜肺乳杆菌中的bbb320种效应蛋白易位到宿主细胞中，以调节过多的细胞过程以产生增殖生态位。由于许多效应器可能已经进化到可以调节原始真核宿主的细胞过程，因此大多数效应器不参与人类巨噬细胞内的细胞内生长就不足为奇了。一些效应器可能调节高度保守的真核生物过程，而其他效应器可能靶向哺乳动物中不存在的原生生物特异性过程。由于缺乏确定效应物在嗜肺乳杆菌适应各种原生生物中的作用的研究，阻碍了确定大多数效应物功能的进展，这些效应物通常在小鼠或人巨噬细胞中进行研究。由于许多原生生物限制嗜肺乳杆菌，利用这些宿主也有助于破译嗜肺乳杆菌无法克服某些原生生物宿主限制的机制。在这里，我们回顾了嗜肺乳杆菌与其容许性和限制性原生宿主的相互作用，并概述了我们在嗜肺乳杆菌与原生宿主相互作用以及嗜肺乳杆菌进化成为人类病原体方面的成就和差距。
Within the human host, Legionella pneumophila replicates within alveolar macrophages, leading to pneumonia. However, L. pneumophila is an aquatic generalist pathogen that replicates within a wide variety of protist hosts, including amoebozoa, percolozoa, and ciliophora. Within the human host, Legionella pneumophila replicates within alveolar macrophages, leading to pneumonia. However, L. pneumophila is an aquatic generalist pathogen that replicates within a wide variety of protist hosts, including amoebozoa, percolozoa, and ciliophora. The intracellular lifestyles of L. pneumophila within the two evolutionarily distant hosts macrophages and protists are remarkably similar. Coevolution with numerous protist hosts has shaped plasticity of the genome of L. pneumophila, which harbors numerous proteins encoded by genes acquired from primitive eukaryotic hosts through interkingdom horizontal gene transfer. The Dot/Icm type IVb translocation system translocates ∼6,000 effectors among Legionella species and >320 effector proteins in L. pneumophila into host cells to modulate a plethora of cellular processes to create proliferative niches. Since many of the effectors have likely evolved to modulate cellular processes of primitive eukaryotic hosts, it is not surprising that most of the effectors do not contribute to intracellular growth within human macrophages. Some of the effectors may modulate highly conserved eukaryotic processes, while others may target protist-specific processes that are absent in mammals. The lack of studies to determine the role of the effectors in adaptation of L. pneumophila to various protists has hampered the progress to determine the function of most of these effectors, which are routinely studied in mouse or human macrophages. Since many protists restrict L. pneumophila, utilization of such hosts can also be instrumental in deciphering the mechanisms of failure of L. pneumophila to overcome restriction of certain protist hosts. Here, we review the interaction of L. pneumophila with its permissive and restrictive protist environmental hosts and outline the accomplishments as well as gaps in our knowledge of L. pneumophila-protist host interaction and L. pneumophila’s evolution to become a human pathogen.