School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, United States.
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, United States.
J Proteome Res. 2022 Jun 3;21(6):1467-1474. doi: 10.1021/acs.jproteome.2c00073. Epub 2022 May 10.
is a common source of hospital-acquired bacterial infections, where the emergence of antibiotic resistance is a serious human health concern. Most investigations into virulence and antibiotic resistance have relied on cultivation conditions and optimized media formulations. However, can survive and adapt to a hostile host environment or antibiotic treatments by rapidly adjusting its metabolic activity. To assess this metabolic response, strains susceptible and nonsusceptible to daptomycin were cultivated in medium supplemented with 55% serum to more closely approximate conditions. Growth analyses, MIC testing, and NMR-based metabolomics determined that serum decreased daptomycin susceptibility and altered metabolism in . Both strains exhibited altered amino acid biosynthesis and catabolism, enhanced fermentation, and a modified salt tolerance response. The observation that growth conditions defined to antibiotics by may be a critical consideration for designing an effective drug discovery study.
是医院获得性细菌感染的常见来源,其中抗生素耐药性的出现是一个严重的人类健康问题。大多数关于毒力和抗生素耐药性的研究都依赖于培养条件和优化的培养基配方。然而,能够通过快速调整其代谢活性来在宿主环境或抗生素治疗中生存和适应。为了评估这种代谢反应,对易感性和非易感性达托霉素的 菌株在补充有 55%血清的培养基中进行培养,以更接近 的条件。生长分析、MIC 测试和基于 NMR 的代谢组学确定,血清降低了达托霉素的敏感性,并改变了 中的代谢。两种 菌株的氨基酸生物合成和分解代谢均发生改变,发酵增强,盐耐受性反应改变。观察到,生长条件可能是设计有效药物发现研究的一个关键考虑因素。