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Aggregation and Binding Substances Enhance Pathogenicity in Rabbit Models of Enterococcus faecalis Endocarditis

机译:聚集和结合物质增强粪肠球菌心内膜炎兔模型的致病性

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We investigated the importance of enterococcal aggregation substance (AS) and enterococcal binding substance (EBS) in rabbit models of Enterococcus faecalis cardiac infections. First, American Dutch belted rabbits were injected intraventricularly with 108 CFU and observed for 2 days. No clinical signs of illness developed in animals given AS? EBS?organisms, and all survived. All rabbits given AS?EBS+ organisms developed signs of illness, including significant pericardial inflammation, but only one of six died. All animals given AS+ EBS? organisms developed signs of illness, including pericardial inflammation, and survived. All rabbits given AS+ EBS+ organisms developed signs of illness and died. None of the rabbits receiving AS+ EBS+ organisms showed gross pericardial inflammation. The lethality and lack of inflammation are consistent with the presence of a superantigen. Rabbit and human lymphocytes were highly stimulated in vitro by cell extracts, but not cell-free culture fluids, of AS+ EBS+ organisms. In contrast, cell extracts from AS? EBS? organisms weakly stimulated lymphocyte proliferation. Culture fluids from human lymphocytes stimulated with AS+/EBS+enterococci contained high levels of gamma interferon and tumor necrosis factor alpha (TNF-α) and TNF-β, which is consistent with functional stimulation of T-lymphocyte proliferation and macrophage activation. Subsequent experiments examined the abilities of the same strains to cause endocarditis in a catheterization model. New Zealand White rabbits underwent transaortic catheterization for 2 h, at which time catheters were removed and animals were injected with 2 × 109 CFU of test organisms. None of the animals given AS? EBS? organisms developed vegetations or showed autopsy evidence of tissue damage. Rabbits given AS? EBS+ or AS+ EBS?organisms developed small vegetations and had splenomegaly at autopsy. All rabbits given AS+ EBS+ organisms developed large vegetations and had splenomegaly and lung congestion at autopsy. Similar experiments that left catheters in place for 3 days revealed that all rabbits given AS? EBS? or AS+ EBS+ organisms developed vegetations, but animals given AS+ EBS+ organisms had larger vegetations and autopsy evidence of lung congestion. These experiments provide direct evidence that these two cell wall components play an important role in the pathogenesis of endocarditis as well as in conjugative plasmid transfer.
机译:我们研究了粪肠球菌心脏感染兔模型中肠球菌聚集物质(AS)和肠球菌结合物质(EBS)的重要性。首先,给美国荷兰带状兔子的脑室内注射10 8 CFU,观察2天。接受AS ? EBS ?生物的动物没有出现疾病的临床症状,并且全部存活。所有接受AS ? EBS + 生物的兔子都出现了疾病迹象,包括明显的心包炎症,但只有六只死亡。所有接受AS + EBS ?生物的动物均出现疾病迹象,包括心包炎,并存活。接受AS + EBS + 生物的所有兔子均出现疾病迹象并死亡。接受AS + EBS + 生物的兔子均未显示严重的心包炎。杀伤力和缺乏炎症与超抗原的存在是一致的。在体外,AS + EBS + 生物的细胞提取物(而非无细胞培养液)对兔和人的淋巴细胞具有高度刺激性。相反,来自AS ? EBS ?生物的细胞提取物对淋巴细胞增殖的刺激较弱。 AS + / EBS + 肠球菌刺激的人淋巴细胞培养液中含有高水平的γ-干扰素和肿瘤坏死因子α(TNF-α)和TNF-β,这是与功能性刺激T淋巴细胞增殖和巨噬细胞活化相一致。随后的实验检查了相同菌株在导管插入模型中引起心内膜炎的能力。新西兰白兔经主动脉导管插入2 h,然后拔出导管,并向动物注射2×10 9 CFU测试生物。接受AS ? EBS ?生物的动物均未发育出植被或尸体组织损伤的证据。给予AS ? EBS + 或AS + EBS ?生物的兔子生长着小的植被,尸体解剖时脾肿大。所有接受AS + EBS + 生物的兔子均生长大,尸体解剖时有脾肿大和肺充血。将导管放置3天的类似实验表明,所有兔子均接受AS ? EBS ?或AS + EBS + 生物体形成了植被,但是使用AS + EBS + 生物体的动物具有较大的植被,并且有尸检的证据表明肺充血。这些实验提供了直接的证据,表明这两个细胞壁成分在心内膜炎的发病机理以及共轭质粒转移中起着重要作用。

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