首页> 外文期刊>Infection and immunity >Both Epsilon-Toxin and Beta-Toxin Are Important for the Lethal Properties of Clostridium perfringens Type B Isolates in the Mouse Intravenous Injection Model
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Both Epsilon-Toxin and Beta-Toxin Are Important for the Lethal Properties of Clostridium perfringens Type B Isolates in the Mouse Intravenous Injection Model

机译:Epsilon毒素和Beta毒素对于小鼠静脉注射模型中产气荚膜梭菌B型分离株的致死特性都很重要

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Clostridium perfringens is capable of producing up to 15 toxins, including alpha-toxin (CPA), beta-toxin (CPB), epsilon-toxin (ETX), enterotoxin, beta2-toxin (CPB2), and perfringolysin O. Type B isolates, which must produce CPA, CPB, and ETX, are associated with animal illnesses characterized by sudden death or acute neurological signs, with or without intestinal damage. Type B pathogenesis in ruminants is poorly understood, with some animals showing lesions and clinical signs similar to those caused by either type C or type D infections. It is unknown whether host or environmental conditions are dominant for determining the outcome of type B disease or if disease outcomes are determined by variable characteristics of type B isolates. To help clarify this issue, 19 type B isolates were evaluated for toxin production during late-log-phase growth via quantitative Western blotting and by biological activity assays. Most type B isolates produced CPB levels similar to those produced by type C isolates in vitro and have the potential to produce genotype C-like disease. The lethality of type B isolate supernatants administered intravenously to mice was evaluated with or without prior trypsin treatment, and monoclonal antibody neutralization studies also were performed. Correlation analyses comparing toxin levels in type B supernatants versus lethality and neutralization studies both found that the main contributor to lethality without pretreatment with trypsin was CPB, whereas neutralization studies indicated that CPB and ETX were both important after trypsin pretreatment. At least part of the CPB produced by type B isolates remained active after trypsin treatment. However, the overall lethalities of most supernatants were lower after trypsin pretreatment. Also, there was a significant association between ETX, CPB2, and CPA production in vitro among type B isolates. However, our results suggest that both CPB and ETX are likely the most important contributors to the pathogenesis of C. perfringens type B infections in domestic animals.
机译:产气荚膜梭菌能够产生多达15种毒素,包括α-毒素(CPA),β-毒素(CPB),ε毒素(ETX),肠毒素,β2-毒素(CPB2)和产气荚膜溶血素O。必须产生CPA,CPB和ETX的B型分离物与动物疾病有关,这些动物疾病的特征在于猝死或急性神经系统症状,有或没有肠道损害。反刍动物的B型发病机理知之甚少,有些动物表现出与C型或D型感染引起的相似的病变和临床体征。尚不清楚宿主或环境条件是否是决定B型疾病结局的主要因素,还是疾病结局是由B型分离株的可变特征决定的。为了帮助澄清这个问题,通过定量蛋白质印迹和生物活性测定法评估了19个B型分离株在对数后期生长期间毒素的产生。大多数B型分离株产生的CPB水平与体外C型分离株产生的CPB水平相似,并且具有产生C型基因病的潜力。在有或没有事先进行胰蛋白酶处理的情况下,评估了静脉内给予小鼠的B型分离物上清液的致死性,并且还进行了单克隆抗体中和研究。比较B型上清液中毒素水平与致死性和中和研究的相关性分析均发现,未经胰蛋白酶预处理的致死性的主要贡献因素是CPB,而中和研究表明,胰蛋白酶预处理后CPB和ETX均很重要。胰蛋白酶处理后,至少部分由B型分离物产生的CPB仍保持活性。但是,胰蛋白酶预处理后,大多数上清液的总体致死率较低。同样,B型分离株之间的体外ETX,CPB2和CPA产生之间存在显着关联。但是,我们的结果表明CPB和ETX可能都是 C发病机理的最重要贡献者。家畜中的产气荚膜B型感染。

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