PDF(Pubmed)
Abstract：
Antimicrobial resistance (AMR) is a significant public health issue that threatens our ability to treat common infections. AMR often emerges in bacteria through upregulation of proteins that allow a subpopulation of resistant bacteria to proliferate through natural selection. Identifying these proteins is crucial for understanding how AMR develops in bacteria and is essential in developing novel therapeutics to combat the threat of widespread AMR. Mass spectrometry-based proteomics is a powerful tool for understanding the biochemical pathways of biological systems, lending remarkable insight into AMR mechanisms in bacteria through measuring the changing protein abundances as a result of antibiotic treatment. Here, we describe a serial passaging method for evolving resistance in bacteria that implements quantitative proteomics to reveal the differential proteomes of resistant bacteria. The focus herein is on antimicrobial peptides (AMPs), but the approach can be generalized for any antimicrobial compound. Comparative proteomics of sensitive vs. resistance strains in response to AMP treatment reveals mechanisms to survive the bioactive compound and points to the mechanism of action for novel AMPs.
摘要：
抗菌素耐药性（AMR）是一个重要的公共卫生问题，威胁着我们治疗常见感染的能力。AMR通常通过蛋白质的上调在细菌中出现,所述蛋白质允许抗性细菌的亚群通过自然选择增殖。鉴定这些蛋白质对于理解AMR如何在细菌中发展至关重要，并且对于开发新型疗法以对抗广泛的AMR威胁至关重要。基于质谱的蛋白质组学是理解生物系统的生化途径的强大工具，通过测量抗生素治疗导致的蛋白质丰度变化，为细菌中的AMR机制提供了非凡的见解。这里,我们描述了一种在细菌中进化抗性的连续传代方法，该方法实现了定量蛋白质组学，以揭示抗性细菌的差异蛋白质组。本文的重点是抗菌肽（AMP），但这种方法可以推广到任何抗菌化合物。敏感性与敏感性的比较蛋白质组学响应AMP处理的抗性菌株揭示了生物活性化合物存活的机制，并指出了新型AMP的作用机制。
