Clostridium perfringens type A is involved in gas gangrene in humans and animals. Following a traumatic injury, rapid bacterial proliferation and exotoxin production result in severe myonecrosis. C. perfringens alpha toxin (CPA) and perfringolysin (PFO) are the main virulence factors responsible for the disease. Recent in vitro studies have identified an Agr-like quorum-sensing (QS) system in C. perfringens that regulates the production of both toxins. The system is composed of an AgrB membrane transporter and an AgrD peptide that interacts with a two-component regulatory system in response to fluctuations in the cell population density. In addition, a synthetic peptide named 6-R has been shown to interfere with this signaling mechanism, affecting the function of the Agr-like QS system in vitro. In the present study, C. perfringens type A strain ATCC 3624 and an isogenic agrB-null mutant were tested in a mouse model of gas gangrene. When mice were intramuscularly challenged with 10⁶ CFU of wild-type ATCC 3624, severe myonecrosis and leukocyte aggregation occurred by 4 h. Similar numbers of an agrB-null mutant strain produced significantly less severe changes in the skeletal muscle of challenged mice. Complementation of the mutant to regain agrB expression restored virulence to wild-type levels. The burdens of all three C. perfringens strains in infected muscle were similar. In addition, animals injected intramuscularly with wild-type ATCC 3624 coincubated with the 6-R peptide developed less severe microscopic changes. This study provides the first in vivo evidence that the Agr-like QS system is important for C. perfringens type A-mediated gas gangrene.

中文翻译：

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类 Agr 的群体感应系统对于产气荚膜梭菌 A 型菌株 ATCC 3624 在小鼠模型中引起气性坏疽很重要。

A 型产气荚膜梭菌与人和动物的气性坏疽有关。外伤后，细菌快速增殖和外毒素产生导致严重的肌坏死。C. perfringens α 毒素 (CPA) 和 perfringolysin (PFO) 是导致该疾病的主要毒力因子。最近的体外研究已经在产气荚膜梭菌中发现了一种类似 Agr 的群体感应 (QS) 系统调节两种毒素的产生。该系统由 AgrB 膜转运蛋白和 AgrD 肽组成，该肽与双组分调节系统相互作用，以响应细胞群密度的波动。此外，一种名为 6-R 的合成肽已被证明会干扰这种信号传导机制，从而在体外影响 Agr 样 QS 系统的功能。在本研究中，产气荚膜梭菌A 型菌株 ATCC 3624 和同基因agrB无效突变体在气性坏疽的小鼠模型中进行了测试。当小鼠用10 ⁶ CFU的野生型ATCC 3624进行肌肉内攻击时，到4小时发生严重的肌坏死和白细胞聚集。相似数量的agrB-null 突变株在受攻击小鼠的骨骼肌中产生的严重变化显着降低。突变体的互补以恢复agrB表达将毒力恢复到野生型水平。受感染肌肉中所有三种产气荚膜梭菌菌株的负担相似。此外，肌肉内注射与 6-R 肽共孵育的野生型 ATCC 3624 的动物发生了不太严重的微观变化。这项研究提供了第一个体内证据，表明 Agr 样 QS 系统对产气荚膜梭菌A 型介导的气性坏疽很重要。