Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors
Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors
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DOI：
10.1007/s00253-005-0040-8
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发表时间：
2006-03-01
影响因子：
5
通讯作者：
Shin, J
中科院分区：
文献类型：
--
作者：
Oh, KB;Oh, MN;Shin, J
分选酶是负责将表面蛋白毒力因子锚定到肽聚糖细胞壁层的革兰氏阳性转肽酶家族。在金黄色葡萄球菌中，分选酶同种型的缺失导致毒力和感染潜力显著降低，使其成为重要的抗毒力靶标。将重组分选酶A（SrtA）和分选酶B（SrtB）与含有LPETG或NPQTN基序的肽底物一起孵育。（Z）-3-（2，5-二甲氧基苯基）-2-（4-甲氧基苯基）丙烯腈、β-谷甾醇-3-O-吡喃葡萄糖苷、盐酸小檗碱和psammaplin A1显示出对SrtA和SrtB的有效抑制活性。这些化合物还表现出对S.金黄色葡萄球菌细胞粘附于纤连蛋白。纤连蛋白结合活性数据突出了这些化合物用于治疗S.金黄色葡萄球菌感染通过抑制分选酶活性。
The sortase enzymes are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus, deletion of the sortase isoforms results in marked reduction in virulence and infection potential, making it an important antivirulence target. Recombinant sortase A (SrtA) and sortase B (SrtB) were incubated with peptide substrate containing either the LPETG or NPQTN motifs. (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, beta-sitosterol-3-O-glucopyranoside, berberine chloride, and psammaplin A1 showed potent inhibitory activity against SrtA and SrtB. These compounds also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The fibronectin-binding activity data highlight the potential of these compounds for the treatment of S. aureus infections via inhibition of sortase activity.