通过Clostridioides difficile中的β-乳酸类抗生素抑制了l,d-转化途径
Ana M Oliveira Paiva1, Pascal Courtin2, Glenn Charpentier1
1Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
iScience
|April 14, 2025
概括
克洛斯特里迪奥伊德复杂菌对类素的耐药性主要不是由于LDT. 相反,类素抑制d,d-carboxypeptidases,影响peptidoglycan组装和突出细菌的适应性.
科学领域:
- 微生物学 微生物学
- 细菌细胞壁的合成.
- 抗生素耐药性 抗生素耐药性
背景情况:
- 困难菌感染是一个重大的健康问题,部分原因是对菌素的耐药性.
- 类素向酸甘 (PG) 组合,这是细菌细胞壁完整性的关键过程.
研究的目的:
- 为了研究Clostridioides difficile.中抗素耐药性的背后机制.
- 阐明l,d-转酶 (LDTs) 和其他酶在PG交叉链接和抗生素耐药性中的作用.
主要方法:
- 分析野生型和突变的C. difficile菌株中的丁糖结构和交叉链接.
- 评估氨酸治疗对PG生物合成途径的影响.
- 研究预测和新型LDT家族的功能.
主要成果:
- 困难菌表现出独特的PG结构,其高比例的3→3交叉链,主要由LDT介导.
- 已知LDT的删除对PG和子皮质完整性产生了最小的影响,这表明了新的LDT的参与.
- 类药物禁用d,d-carboxypeptidases,抑制LDT基质的产生和LD-转途径.
- 青素结合蛋白 (PBPs) 显示在头素治疗期间参与PG交叉链的增加.
结论:
- 在C. difficile中,头素耐药性并非主要由LDT介导.
- 素的d,d-碳酸酶失活是耐药性的关键因素.
- 困难菌在其PG生物合成机制中表现出显著的可塑性,适应抗生素压力.
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