Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis
Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis
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DOI：
10.1016/j.chembiol.2009.04.009
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发表时间：
2009-05-29
影响因子：
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通讯作者：
Brown, Eric D.
中科院分区：
文献类型：
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作者：
D'Elia, Michael A.;Millar, Kathryn E.;Brown, Eric D.
细菌细胞壁一直是著名的抗生素靶点，并为发现新的抗菌化学物质提供了真正的希望。除了肽聚糖外，革兰氏阳性菌的细胞壁还含有大量共价附着于肽聚糖的聚合物磷壁酸。近年来，壁磷壁酸被证明是枯草芽孢杆菌正常形态所必需的，也是金黄色葡萄球菌的重要毒力因子。此外，最近的研究表明。编码磷藻酸生物合成酶的基因的可有可无性是矛盾和复杂的。在这里，我们报道了一种启动子（P-ywaC）的发现，它对磷壁酸合成中的病变敏感。通过化学-遗传方法利用该启动子，我们揭示了去戊烯醇、肽聚糖和磷壁酸生物合成之间令人惊讶的相互作用，这有助于解释磷壁酸基因可缺性的复杂性。此外，新的报告试验代表了一个令人兴奋的途径，发现抗菌分子。
The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for the discovery of new antibacterial chemical matter. In addition to peptidoglycan, the walls of Gram-positive bacteria contain large amounts of the polymer teichoic acid, covalently attached to peptidoglycan. Recently, wall teichoic acid was shown to be essential to the proper morphology of Bacillus subtilis and an important virulence factor for Staphylococcus aureus. Additionally, recent studies have shown that. the dispensability of genes encoding teichoic acid biosynthetic enzymes is paradoxical and complex. Here, we report on the discovery of a promoter (P-ywaC), which is sensitive to lesions in teichoic acid synthesis. Exploiting this promoter through a chemical-genetic approach, we revealed surprising interactions among undecaprenol, peptidoglycan, and teichoic acid biosynthesis that help explain the complexity of teichoic acid gene dispensability. Furthermore, the new reporter assay represents an exciting avenue for the discovery of antibacterial molecules.