摘要

我们的病原体中的抗生素耐药性是药物的气候变化：由人类活动引起，并导致更极端的结果。当抗生素作用于群体内的表型变异时，抗性在微生物群体中出现。这可能源于基因型多样性（由突变或水平基因转移引起），或由于环境变化引起的基因表达差异，称为适应性抗性。适应性变化可以提高适应性，使细菌在更高浓度的抗生素下存活。它们还可以降低适应性，可能导致在较低浓度下选择抗生素抗性。其他环境压力因素有可能以常规检测难以预测的方式促进抗生素耐药性。利用我们之前观察到的常用除草剂可以提高或降低不同抗生素的最低抑菌浓度（MIC），我们首次对假设进行了全面检验，即无论是否使用除草剂，在特定条件下抗生素抗性进化率都会增加增加或减少抗生素MIC。短期进化实验用于各种除草剂和抗生素组合。无论外源性非抗生素剂是否增加或降低抗生素有效性，我们都发现了获得性耐药更频繁出现的情况。这归因于除草剂对MIC或配对抗生素的最小选择性浓度（MSC）的影响。 MSC是抗生素的最低浓度，其中个体的适合度因抗生素而变化，并且低于MIC。我们的研究结果表明，影响细菌之间竞争的其他环境因素可以增强抗生素选择抗生素抗性的能力。我们的工作表明，细菌可能以比实验室条件预测的速度快得多的速度获得环境中的抗生素抗性。

Antibiotic resistance in our pathogens is medicine's climate change: caused by human activity, and resulting in more extreme outcomes. Resistance emerges in microbial populations when antibiotics act on phenotypic variance within the population. This can arise from either genotypic diversity (resulting from a mutation or horizontal gene transfer), or from differences in gene expression due to environmental variation, referred to as adaptive resistance. Adaptive changes can increase fitness allowing bacteria to survive at higher concentrations of antibiotics. They can also decrease fitness, potentially leading to selection for antibiotic resistance at lower concentrations. There are opportunities for other environmental stressors to promote antibiotic resistance in ways that are hard to predict using conventional assays. Exploiting our previous observation that commonly used herbicides can increase or decrease the minimum inhibitory concentration (MIC) of different antibiotics, we provide the first comprehensive test of the hypothesis that the rate of antibiotic resistance evolution under specified conditions can increase, regardless of whether a herbicide increases or decreases the antibiotic MIC. Short term evolution experiments were used for various herbicide and antibiotic combinations. We found conditions where acquired resistance arises more frequently regardless of whether the exogenous non-antibiotic agent increased or decreased antibiotic effectiveness. This is attributed to the effect of the herbicide on either MIC or the minimum selective concentration (MSC) of a paired antibiotic. The MSC is the lowest concentration of antibiotic at which the fitness of individuals varies because of the antibiotic, and is lower than MIC. Our results suggest that additional environmental factors influencing competition between bacteria could enhance the ability of antibiotics to select antibiotic resistance. Our work demonstrates that bacteria may acquire antibiotic resistance in the environment at rates substantially faster than predicted from laboratory conditions.

https://www.ncbi.nlm.nih.gov/pubmed/30345180