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

Autoři: Qianwei Qu aff001;  Jinpeng Wang aff001;  Wenqiang Cui aff001;  Yonghui Zhou aff001;  Xiaoxu Xing aff001;  Ruixiang Che aff001;  Xin Liu aff001;  Xueying Chen aff001;  God’spower Bello-Onaghise aff001;  Chunliu Dong aff001;  Zhengze Li aff003;  Xiubo Li aff004;  Yanhua Li aff001
Působiště autorů: College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, P. R. China aff001;  Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin, Heilongjiang, P. R. China aff002;  Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, P. R. China aff003;  Feed Research Institute Chinese Academy of Agricultural Science, Harbin, Heilongjiang, P. R. China aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226260


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 μg/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 μg/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 μM). In addition, molecular docking was used to predict the binding mode of ISL and IGPD. In vivo tests revealed that, ISL significantly reduced TNF-α 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.

Klíčová slova:

Biofilms – Bovine mastitis – Histidine – Inflammation – Mammary glands – Mastitis – Mouse models – Mutant strains


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