Max Planck Institute for Developmental Biology, Tübingen, Germany.
Institute for Medical Microbiology, University Hospital Tübingen, Tübingen, Germany.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00043-17. Print 2017 Sep.
Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of To investigate the potential for evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two isolates to colistin using a continuous-culture device known as a morbidostat. As a result, colistin resistance reproducibly increased 10-fold within 10 days and 100-fold within 20 days, along with highly stereotypic yet strain-specific mutation patterns. The majority of mutations hit the two-component signaling system and genes involved in lipopolysaccharide (LPS) synthesis, including , , and We tracked the frequencies of all arising mutations by whole-genome deep sequencing every 3 to 4 days to obtain a detailed picture of the dynamics of resistance evolution, including competition and displacement among multiple resistant subpopulations. In 7 out of 18 cultures, we observed mutations in along with a mutator phenotype that seemed to facilitate resistance evolution.
黏菌素是一种最后手段的抗生素，通常用于对抗多种耐药菌株。为了研究对黏菌素产生耐药性的潜力，并绘制黏菌素耐药性的分子靶标，我们使用一种称为病态生物测定仪的连续培养设备，将两种分离株暴露于黏菌素下。结果，在 10 天内，黏菌素耐药性可重复性地增加了 10 倍，在 20 天内增加了 100 倍，同时出现了高度定型但具有菌株特异性的突变模式。大多数突变都发生在双组分信号系统和涉及脂多糖 (LPS) 合成的基因中，包括 、 、和 。我们通过全基因组深度测序，每隔 3 到 4 天跟踪所有出现的突变频率，以获得耐药性进化的详细情况，包括多个耐药亚群之间的竞争和替代。在 18 个培养物中的 7 个中，我们观察到了 中的突变以及似乎有助于耐药性进化的突变体表型。
