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

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01504

DOI=10.3389/fmicb.2020.01504

ISSN=1664-302X

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