Effect of growth rate and selection pressure on rates of transfer of an antibiotic resistance plasmid between E-coli strains
Effect of growth rate and selection pressure on rates of transfer of an antibiotic resistance plasmid between E-coli strains
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DOI：
10.1016/j.plasmid.2014.01.002
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发表时间：
2014-03-01
期刊：
影响因子：
2.6
通讯作者：
ter Kuile, Benno H.
中科院分区：
文献类型：
--
作者：
Schuurmans, Jasper M.;van Hijum, Sacha A. F. T.;ter Kuile, Benno H.
抗生素耐药性增加了医疗保健费用并导致治疗失败。抗性传播的一个重要机制是含有抗性基因的质粒的转移和随后的选择。然而，影响转移率的因素却鲜为人知。在不同选择压力下，在供体和受体菌株的趋化器中共培养质粒转移率。为了证明质粒或受体基因组中的特定突变是否与质粒转移有关，进行了全基因组测序。DM0133 TetR四环素抗性质粒在大肠杆菌K-12菌株之间共培养时转移，频率随着生长速度的增加而增加。转化菌株接管培养的模型表明，在现实中，更多的转移事件发生在低增长率下。在适度的选择压力下，由于抗生素浓度仍然允许生长，最大转移频率确定为每10（11）个细胞分裂一次。在没有四环素或存在高浓度的情况下，转移的频率有时为零，但在其他情况下至少减少五倍。全基因组测序结果表明，质粒在转移过程中没有发生突变，但在转移过程中，受体菌株的基因组发生了两个功能突变。暴露于突变体选择窗口内的抗生素浓度最能刺激抗性质粒的转移。(C) 2014爱思唯尔公司版权所有。
Antibiotic resistance increases costs for health care and causes therapy failure. An important mechanism for spreading resistance is transfer of plasmids containing resistance genes and subsequent selection. Yet the factors that influence the rate of transfer are poorly known. Rates of plasmid transfer were measured in co-cultures in chemostats of a donor and a acceptor strain under various selective pressures. To document whether specific mutations in either plasmid or acceptor genome are associated with the plasmid transfer, whole genome sequencing was performed. The DM0133 TetR tetracycline resistance plasmid was transferred between Escherichia coli K-12 strains during co-culture at frequencies that seemed higher at increased growth rate. Modeling of the take-over of the culture by the transformed strain suggests that in reality more transfer events occurred at low growth rates. At moderate selection pressure due to an antibiotic concentration that still allowed growth, a maximum transfer frequency was determined of once per 10(11) cell divisions. In the absence of tetracycline or in the presence of high concentrations the frequency of transfer was sometimes zero, but otherwise reduced by at least a factor of 5. Whole genome sequencing showed that the plasmid was transferred without mutations, but two functional mutations in the genome of the recipient strain accompanied this transfer. Exposure to concentrations of antibiotics that fall within the mutant selection window stimulated transfer of the resistance plasmid most. (C) 2014 Elsevier Inc. All rights reserved.