Elucidating the Mechanisms of Action of Antimicrobial Agents.
Elucidating the Mechanisms of Action of Antimicrobial Agents.
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尽管抗生素耐药性危机日益严重，但在过去75年 中，新抗菌剂被发现并被批准用于人类的速度迅速下降。使新发现的抗生素超越发现的障碍是阐明它们的作用机制(S)。传统的方法，如亲和纯化和分离抗药性突变体，已被证明是有效的，但并不总是识别靶标的可行选择。最近，依赖于图谱方法的研究出现了爆炸性增长，例如细菌中的热蛋白质组图谱，以更好地了解已发现的抗菌素的机制。在这里，我们概述了靶标去卷积在抗菌药物发现中的重要性，详细介绍了传统的方法，以及识别抗菌靶的方法学的最新进展。
Despite the ever-growing antibiotic resistance crisis, the rate at which new antimicrobials are being discovered and approved for human use has rapidly declined over the past 75 years. A barrier for advancing newly identified antibiotics beyond discovery is elucidating their mechanism(s) of action. Traditional approaches, such as affinity purification and isolation of resistant mutants, have proven effective but are not always viable options for identifying targets. There has been a recent explosion in research that relies on profiling methods, such as thermal proteome profiling in bacteria, for better understanding the mechanisms of discovered antimicrobials. Here, we provide an overview of the importance of target deconvolution in antimicrobial discovery, detailing traditional approaches, as well as the most recent advances in methodologies for identifying antimicrobial targets.
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