肽聚糖
青霉素结合蛋白
金黄色葡萄球菌
脂质Ⅱ
化学
细胞壁
微生物学
青霉素
聚糖
耐甲氧西林金黄色葡萄球菌
细菌
生物化学
抗生素
生物
遗传学
糖蛋白
作者
Veerasak Srisuknimit,Yuan Qiao,Kaitlin Schaefer,Daniel Kahne,Suzanne Walker
摘要
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global public health problem. MRSA strains have acquired a non-native penicillin-binding protein called PBP2a that cross-links peptidoglycan when the native S. aureus PBPs are inhibited by β-lactams. It has been proposed that the native S. aureus PBPs can use cell wall precursors having different glycine branch lengths (penta-, tri-, or monoglycine), while PBP2a can only cross-link peptidoglycan strands bearing a complete pentaglycine branch. This hypothesis has never been tested because the necessary substrates have not been available. Here, we compared the ability of PBP2a and two native S. aureus transpeptidases to cross-link peptidoglycan strands bearing different glycine branches. We show that purified PBP2a can cross-link glycan strands bearing penta- and triglycine, but not monoglycine, and experiments in cells provide support for these findings. Because PBP2a cannot cross-link peptidoglycan containing monoglycine, this study implicates the enzyme (FemA) that extends the monoglycine branch to triglycine on Lipid II as an ideal target for small molecules that restore sensitivity of MRSA to β-lactams.
科研通智能强力驱动
Strongly Powered by AbleSci AI