美国哈佛大学Emily P. Balskus研究团队近日取得一项新成果。经过不懈努力，他们的最新研究提出了代谢组学流程揭示血流感染中的微生物代谢活动。该研究于2024年6月16日发表于国际一流学术期刊《细胞》杂志上。
课题组描述了一个迭代的比较代谢组学流程，以揭示宿主复杂环境中的微生物代谢特征，并将其应用于调查患者的革兰氏阴性血流感染(BSI)。课题组发现在BSI期间细菌衍生的乙酰化多胺水平升高，并发现了负责其生产的酶(SpeG)。阻断SpeG活性可减少细菌增殖并减缓发病。
SpeG活性的降低也增强了细菌膜的通透性，增加了细胞内抗生素的积累，使它们能够在培养和体内克服抗菌素耐药性。该研究强调了在感染自然背景下，研究病原体代谢的工具如何揭示和优先考虑治疗策略，以应对复杂的感染。
据悉，抗菌素耐药性(AMR)的增长凸显了迫切需要确定细菌的致病功能，这些功能可能是临床干预的目标。虽然严重的感染会深刻地改变宿主的代谢，但之前的研究在很大程度上忽略了这方面的微生物代谢。
附：英文原文
Title: A metabolomics pipeline highlights microbial metabolism in bloodstream infections
Author: Jared R. Mayers, Jack Varon, Ruixuan R. Zhou, Martin Daniel-Ivad, Courtney Beaulieu, Amrisha Bholse, Nathaniel R. Glasser, Franziska M. Lichtenauer, Julie Ng, Mayra Pinilla Vera, Curtis Huttenhower, Mark A. Perrella, Clary B. Clish, Sihai D. Zhao, Rebecca M. Baron, Emily P. Balskus
Issue&Volume: 2024-06-16
Abstract: The growth of antimicrobial resistance (AMR) highlights an urgent need to identifybacterial pathogenic functions that may be targets for clinical intervention. Althoughsevere infections profoundly alter host metabolism, prior studies have largely ignoredmicrobial metabolism in this context. Here, we describe an iterative, comparativemetabolomics pipeline to uncover microbial metabolic features in the complex settingof a host and apply it to investigate gram-negative bloodstream infection (BSI) inpatients. We find elevated levels of bacterially derived acetylated polyamines duringBSI and discover the enzyme responsible for their production (SpeG). Blocking SpeGactivity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeGactivity also enhances bacterial membrane permeability and increases intracellularantibiotic accumulation, allowing us to overcome AMR in culture and in vivo. This study highlights how tools to study pathogen metabolism in the natural contextof infection can reveal and prioritize therapeutic strategies for addressing challenging infections.
DOI: 10.1016/j.cell.2024.05.035
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00579-8