在Enterococcus faecium中基于蛋白质的蛋白质分类,以蛋白质的活性为基础,对氨酸化酶和青素结合蛋白进行分类
Jeanette S Grunnvåg1,2, Kristin Hegstad1,2,3, Christian S Lentz1,2
1Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT - The Arctic University of Norway, Postboks 6050 Langnes, 9037 Tromsø, Norway.
FEMS microbes
|May 30, 2024
概括
基于活动的蛋白质分析确定了对抗万胺素耐药的Enterococcus faecium.中的新型可药用血清酸酶标. 这些发现为开发对抗具有挑战性的细菌感染的治疗提供了新的途径.
科学领域:
- 微生物学 微生物学
- 化学蛋白质组学 化学蛋白质组学 化学蛋白质组学
- 药物发现 药物发现 药物发现
背景情况:
- 菌 (Enterococcus faecium) 是一种机会性病原体,抗菌素耐药性日益增加,需要新的治疗点.
- 抗万科米辛菌株构成了严重的治疗挑战.
- 血清酸酶是一种多样化的酶家族,作为药物标的潜力尚未得到充分探索.
研究的目的:
- 通过基于活动的蛋白质概况 (ABPP) 在Enterococcus faecium中识别新的可用药物标.
- 为了研究不同Enterococcus菌株和条件的血清酸酶活性.
- 为了表征以前未经注释的氨酸酸酶在抗万科米辛的E. faecium.中.
主要方法:
- 使用基于活动的蛋白质概况 (ABPP) 与功能化共价抑制剂.
- 使用基于凝的ABPP与博西林-FL一起评估青素结合蛋白 (PBP) 活性.
- 使用广泛反应的光探针 (酸-TMR) 进行氨酸酸酶分析.
- 通过用生物化探针和液态染色体质谱学进行丰富,确定了目标.
主要成果:
- 检测到PBP活动中的应变和条件依赖的变化.
- 在E. faecium clade A1菌株中观察到高氨酸酸酶活性相似性,在A2和E. lactis中变化更大.
- 确定了11种新型的,基本上没有特征的血清酸酶 (例如,α,β-酸酶,SGNH-酸酶,脂酶,氨酸酶,酸酶).
- 这些目标是可用药物治疗的,并且可以在活的抗万科米的E. faecium E745.5中获得.
结论:
- ABPP有效地识别了E. faecium.中的活性酶.
- 发现了新的氨酸酸酶标,可能对E. faecium的生存能力起作用.
- 这些目标代表了开发针对耐药菌株的新抗菌疗法的有希望的候选人.
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