Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.
Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.
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DOI：
10.1186/1741-7015-10-89
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发表时间：
2012-08-13
期刊：
影响因子：
9.3
通讯作者：
Hadany L
中科院分区：
文献类型：
--
作者：
Obolski U;Hadany L
细菌感染中的抗生素耐药性是对公共卫生的日益严重的威胁。最近的证据表明，当暴露在压力条件下时，一些细菌的水平基因转移和突变率更高，从而更快地获得抗生素耐药性。我们将这一新概念纳入医院环境中抗生素多重耐药性出现的数学模型。我们表明，当压力对遗传变异有相当大的影响时，抗生素耐药性的出现会受到显着影响。当遗传变异是压力诱导的时，患者接受抗生素组合（组合）的策略有望促进多重耐药细菌的出现。两种有效药物中的一种随机分配给每位患者（混合）的策略与仅给予一种药物特定时间段（循环）的策略之间的偏好由耐药性获得机制决定。我们讨论了应激影响变异的机制的几个特征，并预测了不同抗生素治疗策略成功的条件。这些发现应该鼓励对应激诱导的遗传变异机制的研究，并建立在考虑抗生素治疗策略时纳入有关这些机制的数据的重要性。
Antibiotic resistance in bacterial infections is a growing threat to public health. Recent evidence shows that when exposed to stressful conditions, some bacteria perform higher rates of horizontal gene transfer and mutation, and thus acquire antibiotic resistance more rapidly. We incorporate this new notion into a mathematical model for the emergence of antibiotic multi-resistance in a hospital setting. We show that when stress has a considerable effect on genetic variation, the emergence of antibiotic resistance is dramatically affected. A strategy in which patients receive a combination of antibiotics (combining) is expected to facilitate the emergence of multi-resistant bacteria when genetic variation is stress-induced. The preference between a strategy in which one of two effective drugs is assigned randomly to each patient (mixing), and a strategy where only one drug is administered for a specific period of time (cycling) is determined by the resistance acquisition mechanisms. We discuss several features of the mechanisms by which stress affects variation and predict the conditions for success of different antibiotic treatment strategies. These findings should encourage research on the mechanisms of stress-induced genetic variation and establish the importance of incorporating data about these mechanisms when considering antibiotic treatment strategies.
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