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高分辨率,高通量检测隐藏的抗生素耐药性与稀释和延迟 (DnD) 敏感性测定

Muqing Ma^1,2, Minsu Kim^3,4,5

¹Department of Physics, Emory University, Atlanta, GA, USA.

Nature communications

|March 7, 2026

概括

一种新的测定方法,稀释和延迟 (DnD),可以检测罕见的抗生素耐药细菌,这些细菌在标准测试中没有被检测到. 这种高分辨率的方法揭示了临床隔离物中常见的,隐藏的耐药性机制,改善了抗生素敏感性测试.

科学领域:

微生物学微生物学
遗传学遗传学是一个
药理学药理学是指药理学的学科.

背景情况:

抗生素耐药性是一个日益增长的全球健康威胁,由遗传和非正规的表型机制驱动.
标准的抗生素敏感性测试往往无法检测出各种表型耐药性,如异型耐药性,持久性和适应性耐药性.
这些局限性阻碍了有效的治疗策略和流行病学监测.

研究的目的:

开发一种可扩展,高分辨率的测试方法,即稀释和延迟 (DnD),能够检测罕见的不敏感药物的细菌细胞.
克服传统敏感性测试在识别多种表型耐药性机制方面的局限性.
为测量和理解抗生素耐药性的新框架提供.

主要方法:

稀释和延迟 (DnD) 试验是基于基本的细菌生长原理开发的.
DnD的实施是为了检测罕见的药物不敏感细胞,其频率低至1亿分之一.
该试验在合成社区,异阻力,持久性和进化进展模型中得到验证,并扩展到临床分离物的高通量测试.

主要成果:

DnD成功检测出罕见的药物不敏感细胞,并提供了大量人群抑制数据 (MIC).
高分辨率数据揭示了由于统计检测极限导致传统测试的局限性.
对临床分离物的DnD高通量应用表明,多药耐药性和耐受性在雷达下普遍存在.

结论:

DnD试验为抗生素敏感性测试提供了前所未有的分辨率和可扩展性.
它为基础研究,临床实践和对抗生素耐药性的流行病学监测提供了强大的工具.
DnD支持一个新的框架,以全面了解抗生素耐药性机制.

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