Bacterial drug tolerance under clinical conditions is governed by anaerobic adaptation but not anaerobic respiration.
Bacterial drug tolerance under clinical conditions is governed by anaerobic adaptation but not anaerobic respiration.
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DOI：
10.1128/aac.02793-14
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发表时间：
2014-10
影响因子：
4.9
通讯作者：
Titball RW
中科院分区：
文献类型：
--
作者：
Hemsley CM;Luo JX;Andreae CA;Butler CS;Soyer OS;Titball RW
非遗传性抗生素耐药性是一种现象，即基因相同的细菌亚群对抗生素表现出表型耐受性。我们在这里显示，与大肠杆菌相比，临床相关的伯克氏菌属显示出更高水平的细胞耐受头孢他啶。通过在模拟体内感染的条件下测量耐药细胞形成的动力学，我们表明，在伯克霍尔德菌中，氧水平影响这些细胞的形成。耐药细胞的特征是无氧代谢特征，可以通过给系统充氧或添加硝酸盐来消除。转录组谱表明，这些细胞不是休眠的持久性细胞，由于厌氧硝酸盐呼吸、外排泵、β-内酰胺酶和应激反应蛋白的上调，它们可能具有耐药能力。这些发现对慢性细菌感染的治疗以及用于体外研究耐药和持久性细胞的方法和条件具有重要意义。
Noninherited antibiotic resistance is a phenomenon whereby a subpopulation of genetically identical bacteria displays phenotypic tolerance to antibiotics. We show here that compared to Escherichia coli, the clinically relevant genus Burkholderia displays much higher levels of cells that tolerate ceftazidime. By measuring the dynamics of the formation of drug-tolerant cells under conditions that mimic in vivo infections, we show that in Burkholderia bacteria, oxygen levels affect the formation of these cells. The drug-tolerant cells are characterized by an anaerobic metabolic signature and can be eliminated by oxygenating the system or adding nitrate. The transcriptome profile suggests that these cells are not dormant persister cells and are likely to be drug tolerant as a consequence of the upregulation of anaerobic nitrate respiration, efflux pumps, β-lactamases, and stress response proteins. These findings have important implications for the treatment of chronic bacterial infections and the methodologies and conditions that are used to study drug-tolerant and persister cells in vitro.