In vitro activity and In vivo efficacy of Isoliquiritigenin against Staphylococcus xylosus ATCC 700404 by IGPD target

文献类型： 外文期刊

第一作者： Qu, Qianwei

作者： Qu, Qianwei;Wang, Jinpeng;Cui, Wenqiang;Zhou, Yonghui;Xing, Xiaoxu;Che, Ruixiang;Liu, Xin;Chen, Xueying;Bello-Onaghise, God'spower;Dong, Chunliu;Li, Yanhua;Qu, Qianwei;Wang, Jinpeng;Cui, Wenqiang;Zhou, Yonghui;Xing, Xiaoxu;Che, Ruixiang;Liu, Xin;Chen, Xueying;Bello-Onaghise, God'spower;Dong, Chunliu;Li, Yanhua;Li, Zhengze;Li, Xiubo

作者机构：

期刊名称：PLOS ONE （ 影响因子：3.24； 五年影响因子：3.788 ）

ISSN： 1932-6203

年卷期： 2019 年 14 卷 12 期

页码：

收录情况： SCI

摘要： Staphylococcus xylosus (S. xylosus) is a type of coagulase-negative Staphylococcus, which was previously considered as non-pathogenic. However, recent studies have linked it with cases of mastitis in cows. Isoliquiritigenin (ISL) is a bioactive compound with pharmacological functions including antibacterial activity. In this study, we evaluated the effect of ISL on S. xylosus in vitro and in vivo. The MIC of ISL against S. xylosus was 80 mu g/mL. It was observed that sub-MICs of ISL (1/2MIC, 1/4MIC, 1/8MIC) significantly inhibited the formation of S. xylosus biofilm in vitro. Previous studies have observed that inhibiting imidazole glycerol phosphate dehydratase (IGPD) concomitantly inhibited biofilm formation in S. xylosus. So, we designed experiments to target the formation of IGPD or inhibits its activities in S. xylosus ATCC 700404. The results indicated that the activity of IGPD and its histidine content decreased significantly under 1/2 MIC (40 mu g/mL) ISL, and the expression of IGPD gene (hisB) and IGPD protein was significantly down-regulated. Furthermore, Bio-layer interferometry experiments showed that ISL directly interacted with IGPD protein (with strong affinity; KD = 234 mu M). In addition, molecular docking was used to predict the binding mode of ISL and IGPD. In vivo tests revealed that, ISL significantly reduced TNF-alpha and IL-6 levels, mitigated the destruction of the mammary glands and reversed the production of inflammatory cells in mice. The results of the study suggest that, ISL may inhibit S. xylosus growth by acting on IGPD, which can be used as a target protein to treat infections caused by S. xylosus.

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