The evolution of no-cost resistance at sub-MIC concentrations of streptomycin in Streptomyces coelicolor
The evolution of no-cost resistance at sub-MIC concentrations of streptomycin in Streptomyces coelicolor
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天蓝色链霉菌在亚 MIC 浓度链霉素下无成本耐药性的演变
DOI：
10.1101/062414
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Westhoff S
中科院分区：
文献类型：
--
作者：
Westhoff S
在药物使用的高浓度下，抗生素对细菌种群产生强烈的选择性，以进化出耐药性。然而，这些致死浓度可能并不代表细菌在土壤中面临的浓度，这一认识导致了抗生素在土壤环境中的作用以及亚致死挑战过程中耐药性演变动态的问题。在这里，我们研究了抗性的演变，以亚最低抑菌浓度（亚MIC）的链霉素在丝状土壤细菌天蓝色链霉菌。首先，我们表明，自发耐药性链霉素导致平均健身赤字约21%的药物的情况下，然而，这些成本被消除的浓度低至1/10的敏感菌株的MIC。使用实验进化，我们接下来表明，当细菌暴露于亚MIC剂量500代时，对>MIC水平的链霉素的抗性容易进化。此外，在亚MIC链霉素浓度下进化的抗性克隆没有健身成本。全基因组分析表明，进化的耐药克隆固定了一些与高药物浓度下分离的相同的突变;然而，所有进化的克隆都携带额外的突变和一些固定的突变，这些突变要么补偿了昂贵的耐药性，要么没有相关的适应性成本。我们的研究结果拓宽了耐药性在自然界中进化的条件，并表明，不是低浓度抗生素作为信号，而是耐药性作为武器而进化。
At the high concentrations used in medicine, antibiotics exert strong selection on bacterial populations for the evolution of resistance. However, these lethal concentrations may not be representative of the concentrations bacteria face in soil, a recognition that has led to questions of the role of antibiotics in soil environments as well as the dynamics of resistance evolution during sublethal challenge. Here we examine the evolution of resistance to sub-minimal inhibitory concentrations (sub-MIC) of streptomycin in the filamentous soil bacteriumStreptomyces coelicolor. First, we show that spontaneous resistance to streptomycin causes an average fitness deficit of ~21% in the absence of drugs; however, these costs are eliminated at concentrations as low as 1/10 the MIC of susceptible strains. Using experimental evolution, we next show that resistance to >MIC levels of streptomycin readily evolves when bacteria are exposed to sub-MIC doses for 500 generations. Furthermore, the resistant clones that evolved at sub-MIC streptomycin concentrations carry no fitness cost. Whole-genome analyses reveal that evolved resistant clones fixed some of the same mutations as those isolated at high drug concentrations; however, all evolved clones carry additional mutations and some fixed mutations that either compensate for costly resistance or have no associated fitness costs. Our results broaden the conditions under which resistance can evolve in nature and suggest that rather than low-concentration antibiotics acting as signals, resistance evolves in response to antibiotics used as weapons.
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DOI：
10.1016/j.bbrc.2013.01.018
发表时间：
2013-02
影响因子：
3.1
作者：
K. Yeo;Eun Hye Kim;E. Hwang;Young-Hyun Han;Y. Eo;H. Kim;O. Kwon;Young-Soo Hong;C. Cheong;H. Cheong
通讯作者：
K. Yeo;Eun Hye Kim;E. Hwang;Young-Hyun Han;Y. Eo;H. Kim;O. Kwon;Young-Soo Hong;C. Cheong;H. Cheong
影响因子：
3.2
作者：
Huang, Tzu-Wen;Chen, Carton W.
通讯作者：
Chen, Carton W.
影响因子：
11.8
作者：
Drlica, Karl;Zhao, Xilin
通讯作者：
Zhao, Xilin
影响因子：
3.2
作者：
Nishimura, Kenji;Hosaka, Takeshi;Ochi, Kozo
通讯作者：
Ochi, Kozo
抗生素生产细菌中耐药基因的环境库及其对抗生素耐药性进化的可能影响
影响因子：
21.1
作者：
P. Laskaris;W. Gaze;E. Wellington
通讯作者：
E. Wellington