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首页> 外文期刊>Infection and immunity >Role of the 85-Kilobase Plasmid and Plasmid-Encoded Virulence-Associated Protein A in Intracellular Survival and Virulence of Rhodococcus equi
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Role of the 85-Kilobase Plasmid and Plasmid-Encoded Virulence-Associated Protein A in Intracellular Survival and Virulence of Rhodococcus equi

机译：85千碱基质粒和质粒编码的毒力相关蛋白A在马红球菌的细胞内存活和毒力中的作用。

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Rhodococcus equi is a facultative intracellular pathogen of macrophages and a cause of pneumonia in young horses (foals) and immunocompromised people. Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb plasmids encoding a highly immunogenic virulence-associated protein (VapA). The objective of this study was to determine the role of the 85-kb plasmid and VapA in the intracellular survival and virulence of R. equi. Clinical isolates containing the plasmid and expressing VapA efficiently replicated within mouse macrophages in vitro, while plasmid-cured derivatives of these organisms did not multiply intracellularly. An isolate harboring the large plasmid also replicated in the tissues of experimentally infected mice, whereas its plasmid-cured derivative was rapidly cleared. All foals experimentally infected with a plasmid-containing clinical isolate developed severe bronchopneumonia, whereas the foals infected with its plasmid-cured derivative remained asymptomatic and free of visible lung lesions. By day 14 postinfection, lung bacterial burdens had increased considerably in foals challenged with the plasmid-containing clinical isolate. In contrast, bacteria could no longer be cultured from the lungs of foals challenged with the isogenic plasmid-cured derivative. A recombinant, plasmid-cured derivative expressing wild-type levels of VapA failed to replicate in macrophages and remained avirulent for both mice and foals. These results show that the 85-kb plasmid of R. equi is essential for intracellular replication within macrophages and for development of disease in the native host, the foal. However, expression of VapA alone is not sufficient to restore the virulence phenotype.
机译： Rhodococcus equi 是巨噬细胞的兼性细胞内病原体，是幼马（驹）和免疫功能低下的人引起肺炎的原因。 R的分离株。肺炎小马驹的马科动物通常含有85kb或90kb的大质粒，编码高度免疫原性的毒力相关蛋白（VapA）。这项研究的目的是确定85 kb质粒和VapA在 R的细胞内存活和毒性中的作用。等。含有质粒并表达VapA的临床分离株可在体外在小鼠巨噬细胞中有效复制，而这些生物的质粒固化衍生物并未在细胞内繁殖。带有大质粒的分离株也可以在实验感染小鼠的组织中复制，而其质粒固化的衍生物可以快速清除。实验上感染了含有质粒的临床分离株的所有小马均发展为严重支气管肺炎，而被其质粒固化的衍生物感染的小马则无症状且无可见的肺部病变。感染后第14天，用含质粒的临床分离株攻击的小马驹的肺细菌负担已大大增加。相反，不再能够从用等基因质粒固化的衍生物攻击的小马驹的肺中培养细菌。表达野生型水平的VapA的重组质粒固化衍生物无法在巨噬细胞中复制，并且对小鼠和小马都无毒。这些结果表明 R的85kb质粒。 equi 对于巨噬细胞内的细胞内复制以及天然宿主小马驹的疾病发展至关重要。但是，单独表达VapA不足以恢复毒力表型。

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