Zhang Jian, Liu Shui, Xia Lining, Wen Zhongmei, Hu Naiyu, Wang Tingting, Deng Xuming, He Jiakang, Wang Jianfeng
Department of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, China.
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Front Microbiol. 2020 Jul 14;11:1504. doi: 10.3389/fmicb.2020.01504. eCollection 2020.
Gas gangrene, caused mainly by the anaerobic bacterium (), causes death within 48 h of onset. Limited therapeutic strategies are available, and it is associated with extremely high mortality. Both alpha toxin (CPA) and perfringolysin O (PFO) are important virulence factors in the development of gas gangrene, suggesting that they are therapeutic targets. Here, we found that verbascoside, a phenylpropanoid glycoside widely distributed in Chinese herbal medicines, could effectively inhibit the biological activity of both CPA and PFO in hemolytic assays. The oligomerization of PFO was remarkably inhibited by verbascoside. Although no antibacterial activity was observed, verbascoside treatment protected Caco-2 cells from the damage caused by CPA and PFO. Additionally, infected mice treated with verbascoside showed significantly alleviated damage, reduced bacterial burden, and decreased mortality. In summary, verbascoside has an effective therapeutic effect against virulence both and by simultaneously targeting CPA and PFO. Our results provide a promising strategy and a potential lead compound for infections, especially gas gangrene.
气性坏疽主要由厌氧菌（）引起，发病后48小时内可导致死亡。可用的治疗策略有限，且其死亡率极高。α毒素（CPA）和产气荚膜梭菌溶血素O（PFO）都是气性坏疽发展过程中的重要毒力因子，这表明它们是治疗靶点。在此，我们发现毛蕊花糖苷，一种广泛分布于中草药中的苯丙素苷，在溶血试验中可有效抑制CPA和PFO的生物活性。毛蕊花糖苷可显著抑制PFO的寡聚化。虽然未观察到抗菌活性，但毛蕊花糖苷处理可保护Caco-2细胞免受CPA和PFO造成的损伤。此外，用毛蕊花糖苷治疗的感染小鼠显示损伤明显减轻、细菌负荷降低且死亡率下降。总之，毛蕊花糖苷通过同时靶向CPA和PFO对 和 的毒力具有有效的治疗作用。我们的结果为 感染，尤其是气性坏疽提供了一种有前景的策略和一种潜在的先导化合物。
