...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Antibiotics: An International Journal >Targeting DXP synthase in human pathogens: Enzyme inhibition and antimicrobial activity of butylacetylphosphonate
【24h】

Targeting DXP synthase in human pathogens: Enzyme inhibition and antimicrobial activity of butylacetylphosphonate

机译：在人类病原体中靶向DXP合酶：丁基乙酰膦酸丁酯的酶抑制和抗菌活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The unique methylerythritol phosphate pathway for isoprenoid biosynthesis is essential in most bacterial pathogens. The first enzyme in this pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase, catalyzes a distinct thiamin diphosphate (ThDP)-dependent reaction to form DXP from D-glyceraldehyde 3-phosphate (D-GAP) and pyruvate and represents a potential anti-infective drug target. We have previously demonstrated that the unnatural bisubstrate analog, butylacetylphosphonate (BAP), exhibits selective inhibition of Escherichia coli DXP synthase over mammalian ThDP-dependent enzymes. Here, we report the selective inhibition by BAP against recombinant DXP synthase homologs from Mycobacterium tuberculosis, Yersinia pestis and Salmonella enterica. We also demonstrate antimicrobial activity of BAP against both Gram-negative and Gram-positive strains (including E. coli, S. enterica and Bacillus anthracis), and several clinically isolated pathogens. Our results suggest a mechanism of action involving inhibition of DXP synthase and show that BAP acts synergistically with established antimicrobial agents, highlighting a potential strategy to combat emerging resistance in bacterial pathogens.
机译：异戊二烯生物合成的独特的甲基赤藓糖醇磷酸途径在大多数细菌病原体中至关重要。该途径中的第一个酶，即1-脱氧-D-木酮糖5-磷酸（DXP）合酶，催化不同的硫胺素二磷酸（ThDP）依赖性反应，由D-甘油醛3-磷酸（D-GAP）和丙酮酸形成DXP。并代表潜在的抗感染药物靶标。我们以前已经证明，非天然的双底物类似物丁基乙酰膦酸丁酯（BAP），对哺乳动物DDP依赖性酶表现出对大肠杆菌DXP合酶的选择性抑制作用。在这里，我们报道了BAP对来自结核分枝杆菌，鼠疫耶尔森菌和肠炎沙门氏菌的重组DXP合酶同源物的选择性抑制。我们还证明了BAP对革兰氏阴性和革兰氏阳性菌株（包括大肠杆菌，肠炎沙门氏菌和炭疽芽孢杆菌）以及几种临床分离的病原体的抗菌活性。我们的结果提出了一种涉及抑制DXP合酶的作用机制，并表明BAP与已建立的抗菌剂具有协同作用，突出了对抗细菌病原体中新出现的耐药性的潜在策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号