A High-Throughput Molecular Platform for Antimicrobial Discovery and Study

项目摘要。 在抗药性细菌感染率持续上升的同时，我们开发了新的抗菌剂 特工们已经停滞不前。新的候选化合物的高失败率要求开发 发现新的抗菌剂的替代管道，以防止我们滑回抗生素之前的状态 医学时代。我们这项提议的目标是开发和实施一种新的药物分子方法。 筛选对抗生素耐药具有抗菌活性的多肽化学进行深入研究 革兰氏阴性细菌病原体。我们的平台为单个细菌和 在混合细菌种群中，在生理相关条件下相互作用的多肽序列。 裂解事件使用下一代测序进行测量，允许快速和批量筛选数百万 在一个试管中的多肽。这一提议为抗菌肽研究提供了一个巨大的飞跃。 计划工作的完成预计将产生积极的翻译影响，大大扩大我们的 了解具有抗菌活性的多肽化学并寻找新的治疗细菌靶点 靶向，这两者都可能支持开发新的抗菌剂和抗击方法 抗药性细菌。

Project Summary. While rates of antibiotic resistance bacterial infections continue to rise, our development of new antimicrobial agents has stagnated. The high failure rate of new candidate compounds demands the development of alternative pipelines for the discovery of new antimicrobial agents to prevent our slide back to the pre-antibiotic medical era. Our objective in this proposal is to develop and implement a new molecular approach to drug screening for an in-depth study of peptide chemistry with antimicrobial activity against antibiotic-resistant, Gram-negative bacterial pathogens. Our platform creates microenvironments for individual bacteria and peptide sequences to interact under physiologically relevant conditions, within a mixed bacterial population. Lytic events are measured using next-generation sequencing, allowing rapid and batch screening of millions of peptides in one tube. This proposal offers a quantum leap forward in antimicrobial peptide research. Completion of the planned work is expected to have a positive translational impact by greatly expanding our understanding of peptide chemistry with antimicrobial activity and identify new bacterial targets for therapeutic targeting, both of which will likely support the development of new antimicrobials and approaches to fight antibiotic-resistant bacteria.