Exploiting new drug targets in extremely resistant M.abscessus by using small molecule Lipid II binders

摘要 公众越来越面临新出现的传染病的风险。耐药细菌的流行 病原体使目前的抗生素无效，因此必须使用新的药物。 用来对抗这些病原体引起的感染脂质II是细菌生长的重要前体， 膜生物发生和一个已建立的，但未充分利用的目标，目前在临床上的抗生素 使用.我们首次确定了小分子脂质II结合剂，基于相互作用 防御素，天然抗菌肽家族和脂质II之间的关系。表征 有前途的Lipid II结合剂显示，它独特地结合Lipid II，并具有有效的抗肿瘤活性。 分枝杆菌。该提案旨在验证和优化合成Lipid II粘合剂作为一种新的类别 抗生素化合物来对抗这些难以治疗的细菌引起的致病性感染。

Abstract The public is increasingly at risk to emerging infectious diseases. The prevalence of resistant bacterial pathogens is rendering current antibiotics ineffective, and making it essential that new drugs be developed to fight infections caused by these agents. Lipid II is an essential precursor in bacterial membrane biogenesis and an established, yet underutilized target for antibiotics currently in clinical use. We have for the first time identified small molecule Lipid II binders, based on the interaction between defensins, a family of natural antimicrobial peptides and Lipid II. Characterization of promising Lipid II binders reveals that it uniquely binds to Lipid II and has potent activty against Mycobacteria. This proposal aims to validate and optimize synthetic Lipid II binders as a novel class of antibiotic compounds to combat pathogenic infections caused by these hard-to-treat bacteria.