Zhang Bing, Wang Xiyan, Wang Lin, Chen Shuiye, Shi Dongxue, Wang Hongsu
College of Food Science and Engineering, Jilin University, Changchun 130062, China.
College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Molecules. 2016 Oct 26;21(11):1428. doi: 10.3390/molecules21111428.
The intractability of bacterial resistance presents a dilemma for therapies against () 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 infection via targeting SrtA.
细菌耐药性的顽固性给针对（）感染的治疗带来了两难困境。鉴于耐药菌株的不断增多，迫切需要有效的抗毒力策略。分选酶A（SrtA）是一种锚定与毒力相关的表面蛋白的酶，其抑制剂被认为是对抗细菌感染的有前景的候选药物。在本研究中，已检测了干酪素ABBA（ABBA）对SrtA的抑制作用及其分子基础。采用荧光共振能量转移（FRET）分析来确定ABBA对SrtA的抑制活性。为了确定这种活性背后的机制，应用了分子动力学模拟和诱变分析，结果表明，ABBA通过与V166和V168结合直接作用于SrtA，显著减弱了SrtA的催化活性。综上所述，这些发现表明ABBA是一种通过靶向SrtA治疗（）感染的潜在新型抗菌剂。
