Niclosamide as a repurposing drug against Gram-positive bacterial infections

文献类型： 外文期刊

第一作者： Zhang, Wei

作者： Zhang, Wei;Ran, Jinxin;Shang, Lu;Zhang, Lifang;Wang, Mi;Fei, Chenzhong;Chen, Chan;Gu, Feng;Liu, Yingchun;Zhang, Wei;Ran, Jinxin;Shang, Lu;Zhang, Lifang;Wang, Mi;Fei, Chenzhong;Chen, Chan;Gu, Feng;Liu, Yingchun

作者机构：

期刊名称：JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY （ 影响因子：5.758； 五年影响因子：6.051 ）

ISSN： 0305-7453

年卷期： 2022 年 77 卷 12 期

页码：

收录情况： SCI

摘要： Objectives Niclosamide is commonly used as an antiparasitic drug in veterinary clinics. The objectives of this study were to evaluate the efficacy of niclosamide against resistant Gram-positive bacteria in vitro and in an in vivo experimental model of topical bacterial infection. Moreover, to study the antibacterial mechanism of niclosamide to Staphylococcus aureus. Methods A mouse topical infection model was established to detect the antibacterial activity of niclosamide in vivo. The antimicrobial mechanism was probed by visualizing the bacterial morphologies using scanning electron microscopy and transmission electron microscopy. Moreover, the haemolytic assay and western blotting analysis were performed to evaluate whether niclosamide could inhibit the secretion of alpha-haemolysin (alpha-HL) from S. aureus. Results The MICs of niclosamide were below 0.5 mg/L for Gram-positive bacteria, showing excellent antibacterial activity in vitro. The in vivo antibacterial activity results indicated that niclosamide treatment at 10 mg/kg of body weight caused a significant reduction in the abscess area and the number of S. aureus cells. Moreover, the antibacterial mechanism of niclosamide showed that the surface morphology of S. aureus displayed noticeable shrinkage, with an increasing number of small vacuole-like structures observed as the drug concentration increased. Intracellular ATP levels were found to decrease in a niclosamide dose-dependent manner. Haemolysis and western blotting analyses revealed that niclosamide inhibited the haemolytic activity of S. aureus by inhibiting alpha-HL expression under subinhibitory concentration conditions. Conclusions Niclosamide has significant potential for development into drugs that prevent and treat diseases caused by Gram-positive bacteria such as Staphylococcus and Streptococcus.

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