Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A.
Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A.
复制标题
DOI：
10.3390/toxins10100385
复制
发表时间：
2018-09-23
期刊：
影响因子：
4.2
通讯作者：
Yin L
中科院分区：
文献类型：
--
作者：
Ouyang P;He X;Yuan ZW;Yin ZQ;Fu H;Lin J;He C;Liang X;Lv C;Shu G;Yuan ZX;Song X;Li L;Yin L
随着多重耐药金黄色葡萄球菌感染的不断出现和广泛传播，临床上常用抗生素对这些感染的治疗已经无效。抗毒力策略可能是治疗耐药细菌感染的新的、有效的策略。分选酶A（srtA）是革兰氏阳性菌的一种转肽酶，能锚定在革兰氏阳性菌致病过程中起重要作用的表面蛋白。SrtA被认为是治疗细菌感染的潜在的抗毒性药物靶标。本研究发现，毛兰素是一种天然的二苄基化合物，在体外对srtA有抑制作用，半数抑制浓度（IC 50）为20.91 ± 2.31 μg/mL，65.7 ± 7.2 μM，在亚最低抑菌浓度（MIC）为512 μg/mL时，对srtA有抑制作用。 aureus)具有良好的抗菌活性。毛兰素抑制srtA活性的分子机制为：毛兰素与srtA的Ile 182、Val 193、Trp 194、Arg 197和Ile 199残基通过疏水作用形成稳定的结合。此外，S.毛兰素可抑制金黄色葡萄球菌与纤连蛋白的结合和生物膜的形成。金黄色。毛兰素在体内可提高感染S.金黄色葡萄球菌。结果表明毛兰素是一种潜在的抗S.通过影响srtA感染金黄色葡萄球菌。
With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA.
登录
查看更多内容
影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
影响因子：
4.8
作者：
Bentley, Matthew L.;Gaweska, Helena;McCafferty, Dewey G.
通讯作者：
McCafferty, Dewey G.
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.
DOI：
10.1073/pnas.080520697
发表时间：
2000-05-09
影响因子：
11.1
作者：
Mazmanian, SK;Liu, G;Schneewind, O
通讯作者：
Schneewind, O
影响因子：
5
作者：
Oh, KB;Oh, MN;Shin, J
通讯作者：
Shin, J