Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A

Molecules

Bing Zhang¹  Hongsu Wang¹  Xiyan Wang²  Shuiye Chen²  Lin Wang²  Dongxue Shi² 

[1] College of Food Science and Engineering, Jilin University, Changchun 130062, China;College of Veterinary Medicine, Jilin University, Changchun 130062, China;

关键词: Staphylococcus aureus;    sortase A;    dryocrassin;    molecular simulations;   

DOI  :  10.3390/molecules21111428

来源: DOAJ

【 摘 要 】

The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent for S. aureus infection via targeting SrtA.

【 授权许可】

Unknown