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嗜肺军团菌特定生命阶段的病理代谢

The life stage-specific pathometabolism of Legionella pneumophila.

作者信息

Eisenreich Wolfgang, Heuner Klaus

机构信息

Lehrstuhl für Biochemie, Technische Universität München, Germany.

Cellular Interactions of Bacterial Pathogens, ZBS 2, Robert Koch Institute, Berlin, Germany.

出版信息

FEBS Lett. 2016 Nov;590(21):3868-3886. doi: 10.1002/1873-3468.12326. Epub 2016 Aug 18.

Abstract

The genus Legionella belongs to Gram-negative bacteria found ubiquitously in aquatic habitats, where it grows in natural biofilms and replicates intracellularly in various protozoa (amoebae, ciliates). L. pneumophila is known as the causative agent of Legionnaires' disease, since it is also able to replicate in human alveolar macrophages, finally leading to inflammation of the lung and pneumonia. To withstand the degradation by its host cells, a Legionella-containing vacuole (LCV) is established for intracellular replication, and numerous effector proteins are secreted into the host cytosol using a type four B secretion system (T4BSS). During intracellular replication, Legionella has a biphasic developmental cycle that alternates between a replicative and a transmissive form. New knowledge about the host-adapted and life stage-dependent metabolism of intracellular L. pneumophila revealed a bipartite metabolic network with life stage-specific usages of amino acids (e.g. serine), carbohydrates (e.g. glucose) and glycerol as major substrates. These metabolic features are associated with the differentiation of the intracellular bacteria, and thus have an important impact on the virulence of L. pneumophila.

摘要

军团菌属属于革兰氏阴性菌,广泛存在于水生栖息地,在天然生物膜中生长,并在各种原生动物(变形虫、纤毛虫)内进行细胞内复制。嗜肺军团菌是军团病的病原体,因为它也能够在人类肺泡巨噬细胞中复制,最终导致肺部炎症和肺炎。为了抵御宿主细胞的降解作用,军团菌会形成一个含军团菌的液泡(LCV)用于细胞内复制,并利用IV型B分泌系统(T4BSS)将大量效应蛋白分泌到宿主细胞质中。在细胞内复制过程中,军团菌具有双相发育周期,在复制型和传播型之间交替。关于细胞内嗜肺军团菌适应宿主和依赖生命阶段的代谢的新知识揭示了一个二分代谢网络,其中氨基酸(如丝氨酸)、碳水化合物(如葡萄糖)和甘油作为主要底物在生命阶段具有特定的用途。这些代谢特征与细胞内细菌的分化有关,因此对嗜肺军团菌的毒力有重要影响。

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