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基于临床分离株 D-4968 的基因组序列分析鉴定出嗜肺军团菌编码的毒力因子。

Virulence factors encoded by Legionella longbeachae identified on the basis of the genome sequence analysis of clinical isolate D-4968.

机构信息

Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

J Bacteriol. 2010 Feb;192(4):1030-44. doi: 10.1128/JB.01272-09. Epub 2009 Dec 11.

Abstract

Legionella longbeachae causes most cases of legionellosis in Australia and may be underreported worldwide due to the lack of L. longbeachae-specific diagnostic tests. L. longbeachae displays distinctive differences in intracellular trafficking, caspase 1 activation, and infection in mouse models compared to Legionella pneumophila, yet these two species have indistinguishable clinical presentations in humans. Unlike other legionellae, which inhabit freshwater systems, L. longbeachae is found predominantly in moist soil. In this study, we sequenced and annotated the genome of an L. longbeachae clinical isolate from Oregon, isolate D-4968, and compared it to the previously published genomes of L. pneumophila. The results revealed that the D-4968 genome is larger than the L. pneumophila genome and has a gene order that is different from that of the L. pneumophila genome. Genes encoding structural components of type II, type IV Lvh, and type IV Icm/Dot secretion systems are conserved. In contrast, only 42/140 homologs of genes encoding L. pneumophila Icm/Dot substrates have been found in the D-4968 genome. L. longbeachae encodes numerous proteins with eukaryotic motifs and eukaryote-like proteins unique to this species, including 16 ankyrin repeat-containing proteins and a novel U-box protein. We predict that these proteins are secreted by the L. longbeachae Icm/Dot secretion system. In contrast to the L. pneumophila genome, the L. longbeachae D-4968 genome does not contain flagellar biosynthesis genes, yet it contains a chemotaxis operon. The lack of a flagellum explains the failure of L. longbeachae to activate caspase 1 and trigger pyroptosis in murine macrophages. These unique features of L. longbeachae may reflect adaptation of this species to life in soil.

摘要

长滩军团菌是导致澳大利亚军团病的主要病原体,但由于缺乏长滩军团菌特异性诊断检测方法,该菌可能在全球范围内被低估。与嗜肺军团菌相比,长滩军团菌在细胞内运输、半胱天冬酶 1 激活和感染的小鼠模型中表现出明显的差异,但这两种物种在人类中的临床表现却无法区分。与其他军团菌不同的是,长滩军团菌主要存在于潮湿的土壤中,而不是淡水系统中。在本研究中,我们对来自俄勒冈州的长滩军团菌临床分离株 D-4968 进行了测序和注释,并将其与之前发表的嗜肺军团菌基因组进行了比较。结果表明,D-4968 基因组大于嗜肺军团菌基因组,且基因排列顺序与嗜肺军团菌基因组不同。编码 II 型、IV 型 Lvh 和 IV 型 Icm/Dot 分泌系统结构成分的基因是保守的。相比之下,D-4968 基因组中仅发现了 42/140 个编码嗜肺军团菌 Icm/Dot 底物的同源基因。长滩军团菌编码了许多具有真核生物基序和该物种特有的真核蛋白的蛋白,包括 16 个锚蛋白重复蛋白和一种新型 U -box 蛋白。我们预测这些蛋白是通过长滩军团菌 Icm/Dot 分泌系统分泌的。与嗜肺军团菌基因组不同的是,长滩军团菌 D-4968 基因组不包含鞭毛生物合成基因,但它包含一个趋化操纵子。缺乏鞭毛可以解释长滩军团菌无法激活半胱天冬酶 1 并在鼠巨噬细胞中引发细胞焦亡的原因。长滩军团菌的这些独特特征可能反映了该物种对土壤生活的适应。

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