鸢尾黄素作为MgrA抑制剂对小鼠金黄色葡萄球菌肺炎的治疗作用

doi:10.16431/j.cnki.1671-7236.2021.07.038

Abstract

Abstract: The purpose of this study was to screen out the monomer inhibitors of Staphylococcus aureus transcriptional regulator MgrA from the small molecule library of traditional Chinese medicine,and explore its effect on the main virulence factors of Staphylococcus aureus and its therapeutic effect on Staphylococcus aureus-induced pneumonia in mice.Fluorescence anisotropy analysis method was used to screen inhibitors,Real-time PCR,hemolysis test and fibrinogen adhesion test were used to investigate the transcriptional expression of related virulence genes regulated by MrgA and the inhibitory effect on hemolysis and adhesion.The thermal stable migration experiment was used to preliminarily explore its inhibitory mechanism.Finally,a mouse pneumonia model was established to evaluate the therapeutic effect of Tectorigenin on Staphylococcus aureus-induced pneumonia in mice.The results showed that Tectorigenin,as an inhibitor of MgrA,could significantly inhibit the activity of MgrA at a low concentration (IC₅₀=20.35 μg/mL) that did not affect bacterial growth (P<0.05).Real-time PCR results proved that Tectorigenin significantly reduced the transcription levels of fnba gene (P<0.05), extremely significantly reduced the transcription levels of hla and RNAⅢ genes (P<0.01),and at the same time extremely significantly increased the transcription levels of ebh, srap and spa genes (P<0.01).Hemolysis experiments showed that Tectorigenin could extremely significantly inhibit the hemolysis of USA300 strain at a concentration of 8 μg/mL (P<0.01).Fibrinogen adhesion experiments confirmed that Tectorigenin extremely significantly inhibited the adhesion activity of USA300 strain at 32 μg/mL (P<0.01).Thermal shift assay revealed that Tectorigenin inhibited its activity by binding to MgrA.The results of mouse pneumonia experiments showed that Tectorigenin could extremely significantly improve the survival rate of mice infected with Staphylococcus aureus (P<0.01),reduce the amount of bacteria in their lungs (P<0.01), and reduce the pathological damage and inflammation of lung tissue in mouse.The above results indicated that Tectorigenin could treat mouse pneumonia caused by Staphylococcus aureus by inhibiting the activity of the transcriptional regulator MgrA.Tectorigenin could be used as a lead compound for the development of treatment of Staphylococcus aureus infection,and provided a theoretical basis for the development of drugs targeting MgrA.

Key words: Tectorigenin; Staphylococcus aureus; MgrA; inhibitor; mice pneumonia

CLC Number:

S853.7

SU Liyan, WANG Li, WU Jiaqi, GUAN Shuhan, WANG Dacheng, WANG Lin. Therapeutic Effect of Tectorigenin as MgrA Inhibitor on Staphylococcus aureus-induced Pneumonia in Mice[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(7): 2617-2626.

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Therapeutic Effect of Tectorigenin as MgrA Inhibitor on Staphylococcus aureus-induced Pneumonia in Mice

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