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

Abstract

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.

Effect of Syringopicroside Extracted from Syringa oblata Lindl on the Biofilm Formation of Streptococcus suis

“…The glass was stored in a refrigerator at −20 °C, and then it was dried in a Freeze dryer (ES-2030, HITACHI, Tokyo, Japan) for 4 h. The glass was fixed on the sample table with conductive tape and coated the gold film with a thickness of 100–150 Å using an ion sputtering coater (E1010, HITACHI, Tokyo, Japan). Finally, the observation of S. suis biofilm was carried out under an electron microscopy (S-3400N, HITACHI, Tokyo, Japan), which is referred to in a previous study [ 58 ].…”

Rutin, A Natural Inhibitor of IGPD Protein, Partially Inhibits Biofilm Formation in Staphylococcus xylosus ATCC700404 in vitro and in vivo

“…Anti-IGPD polyclonal antibody was obtained from our previous studies ( Qu et al, 2019 ). The effect of 0.8 mg/ml rutin on the expression of IGPD in S. xylosus was also investigated.…”

“…Quantification of the histidine in the sonicated treated bacteria was done in HPLC at 205 nm against concentration using the external standard method. The specific details of the complex system have been previously described ( Qu et al, 2019 ).…”

Antibacterial and Immunotropic Properties of Isoliquiritigenin in Generalized Staphylococcal Infection in Mice

“…Исследования последних лет демонстрируют, что флавоноиды корней солодки увеличивают секрецию IL-17 активированными T-клетками in vitro [6], а также приводят к переключению иммунного ответа с дифференцировкой клеток, продуцирующих IL-17 в модели контактной чувствительности [7]. Более того, в модели генерализованной стафилококковой инфекции предварительное введение суммы флавоноидов солодки увеличивало выживаемость лабораторных животных [8].…”

“…Изоликвиритигенин (ИЛГ) -один из основных флавоноидов корней солодки, обладающий различными видами фармакологической активности: противоопухолевой [9], антимикробной [6], а также противовоспалительной и иммуномодулирующей [9][10][11], что обуславливает актуальность исследования его в качестве агента при генерализованном инфекционно-воспалительном процессе. В настоящем исследовании нами предпринята попытка экспериментального обоснования применения халкона изоликвиритигенина (ИЛГ) при генерализованной инфекции мышей, вызванной S. aureus.…”