Brown Stephanie, Zhang Yu-Hui, Walker Suzanne
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Chem Biol. 2008 Jan;15(1):12-21. doi: 10.1016/j.chembiol.2007.11.011.
Resistance to every family of clinically used antibiotics has emerged, and there is a pressing need to explore unique antibacterial targets. Wall teichoic acids (WTAs) are anionic polymers that coat the cell walls of many Gram-positive bacteria. Because WTAs play an essential role in Staphylococcus aureus colonization and infection, the enzymes involved in WTA biosynthesis are proposed to be targets for antibiotic development. To facilitate the discovery of WTA inhibitors, we have reconstituted the intracellular steps of S. aureus WTA biosynthesis. We show that two intracellular steps in the biosynthetic pathway are different from what was proposed. The work reported here lays the foundation for the discovery and characterization of inhibitors of WTA biosynthetic enzymes to assess their potential for treating bacterial infections.
对临床上使用的各类抗生素的耐药性已经出现，因此迫切需要探索独特的抗菌靶点。壁磷壁酸（WTA）是一种覆盖许多革兰氏阳性菌细胞壁的阴离子聚合物。由于WTA在金黄色葡萄球菌的定植和感染中起重要作用，参与WTA生物合成的酶被认为是抗生素开发的靶点。为了促进WTA抑制剂的发现，我们重构了金黄色葡萄球菌WTA生物合成的细胞内步骤。我们发现生物合成途径中的两个细胞内步骤与之前提出的不同。本文报道的工作为发现和鉴定WTA生物合成酶抑制剂奠定了基础，以评估它们治疗细菌感染的潜力。
