Verbascoside Protects Mice From Clostridial Gas Gangrene by Inhibiting the Activity of Alpha Toxin and Perfringolysin O

Jian Zhang; Shui Liu; Lining Xia; Zhongmei Wen; Naiyu Hu; Tingting Wang; Xuming Deng; Jiakang He; Jianfeng Wang

doi:10.3389/fmicb.2020.01504

Verbascoside Protects Mice From Clostridial Gas Gangrene by Inhibiting the Activity of Alpha Toxin and Perfringolysin O

Front Microbiol. 2020 Jul 14:11:1504. doi: 10.3389/fmicb.2020.01504. eCollection 2020.

Authors

Jian Zhang^{1

2}, Shui Liu^{1

2}, Lining Xia³, Zhongmei Wen¹, Naiyu Hu¹, Tingting Wang^{1

2}, Xuming Deng^{1

2}, Jiakang He^{1

4}, Jianfeng Wang^{1

2}

Affiliations

¹ Department of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, China.
² Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
³ College of Veterinary Medicine, Xinjiang Agricultural University, Ürümqi, China.
⁴ College of Animal Science and Technology, Guangxi University, Nanning, China.

Abstract

Gas gangrene, caused mainly by the anaerobic bacterium Clostridium perfringens (C. perfringens), causes death within 48 h of onset. Limited therapeutic strategies are available, and it is associated with extremely high mortality. Both C. perfringens 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 C. perfringens virulence both in vitro and in vivo by simultaneously targeting CPA and PFO. Our results provide a promising strategy and a potential lead compound for C. perfringens infections, especially gas gangrene.

Keywords: Clostridium perfringens; alpha toxin; anti-infection; gas gangrene; perfringolysin O; verbascoside.