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马红球菌的发病机制与毒力

Pathogenesis and virulence of Rhodococcus equi.

作者信息

Hondalus M K

机构信息

Howard Hughes Medical Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

出版信息

Vet Microbiol. 1997 Jun 16;56(3-4):257-68. doi: 10.1016/s0378-1135(97)00094-1.

DOI:10.1016/s0378-1135(97)00094-1
PMID:9226840
Abstract

Inhalation of the soil-borne organism, Rhodococcus equi, can lead to a chronic and severe pyogranulomatous pneumonia in young horses and immunocompromised people. In addition, ulcerative colitis is a common sequela to infection in foals, and dissemination from the lung to other body sites is not uncommon in either the horse or man. Although the facultative intracellular bacterium is susceptible to neutrophil-mediated killing, it is able to resist innate macrophage defenses and establish residence within the intracellular environment of that phagocyte. Definitive virulence factors of R. equi have not yet been determined, but potential candidates include capsular polysaccharide, the exoenzyme cholesterol oxidase, cell wall mycolic acids, and the products encoded by a virulence-associated plasmid. The ability to replicate within the macrophage is associated with virulence, and correlates in animals with the possession of a large plasmid and expression of the plasmid-encoded, surface-expressed lipoprotein, VapA. All strains of R. equi isolated from horses with clinical disease possess a large plasmid and express VapA antigens. In addition, bacterial clearance and granuloma development in mice is linked to plasmid possession and VapA expression. Plasmid containing strains replicate within the tissues of the mouse. whereas plasmid-cured strains are rapidly cleared. At present, the function of the VapA protein is unknown. In contrast to what is observed in the foal, only a small percentage of R. equi strains isolated from humans with rhodococcal disease express VapA antigens, although a high proportion of others express a related protein which is associated with reduced virulence and is also plasmid-encoded. In a limited number of plasmid-negative human isolates, virulence has been linked to beta-lactam resistance, and preliminary evidence suggests that the phenotype may be phage encoded. It is likely that the immune status of the patient can influence whether a particular strain of R. equi is able to produce clinical disease, and certainly experimental infection in mice has confirmed that an intact cellular immune response is necessary for clearance of the organism.

摘要

吸入土壤传播的马红球菌可导致幼马和免疫功能低下的人发生慢性重症脓性肉芽肿性肺炎。此外,溃疡性结肠炎是幼驹感染后的常见后遗症,在马和人中,该菌从肺部扩散到身体其他部位的情况并不少见。尽管这种兼性胞内菌易受中性粒细胞介导的杀伤,但它能够抵抗先天性巨噬细胞防御,并在吞噬细胞的细胞内环境中定居。马红球菌的确切毒力因子尚未确定,但潜在的候选因子包括荚膜多糖、外酶胆固醇氧化酶、细胞壁分枝菌酸以及毒力相关质粒编码的产物。在巨噬细胞内复制的能力与毒力相关,在动物中与拥有大质粒以及质粒编码的表面表达脂蛋白VapA的表达相关。从患有临床疾病的马中分离出的所有马红球菌菌株都拥有大质粒并表达VapA抗原。此外,小鼠体内细菌的清除和肉芽肿的形成与质粒的拥有和VapA的表达有关。含有质粒的菌株在小鼠组织内复制,而质粒清除的菌株则被迅速清除。目前,VapA蛋白的功能尚不清楚。与在幼驹中观察到的情况相反,从患有红球菌病的人类中分离出的马红球菌菌株中,只有一小部分表达VapA抗原,尽管其他很大一部分表达一种与毒力降低相关的相关蛋白,该蛋白也是质粒编码的。在数量有限的质粒阴性人类分离株中,毒力与β-内酰胺耐药性有关,初步证据表明该表型可能是噬菌体编码的。患者的免疫状态可能会影响特定的马红球菌菌株是否能够引发临床疾病,而且小鼠实验感染已证实,完整的细胞免疫反应对于清除该菌是必要的。

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