Sublethal exposure to commercial formulations of the herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium.
Sublethal exposure to commercial formulations of the herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium.
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DOI：
10.1128/mbio.00009-15
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发表时间：
2015-03-24
期刊：
影响因子：
6.4
通讯作者：
Heinemann JA
中科院分区：
文献类型：
--
作者：
Kurenbach B;Marjoshi D;Amábile-Cuevas CF;Ferguson GC;Godsoe W;Gibson P;Heinemann JA
杀生物剂，如除草剂，通常测试毒性，但不测试对微生物的亚致死作用。已知许多杀生物剂诱导适应性多重抗生素抗性表型。这可能是由于外排泵的表达增加，外膜孔蛋白的合成减少，或两者兼而有之。大肠杆菌和鼠伤寒沙门氏菌暴露于三种除草剂的商业制剂-麦草畏（Kamba），2，4-二氯苯氧乙酸（2，4-D）和草甘膦（Roundup）-被发现诱导对抗生素的反应发生变化。在存在和不存在亚致死浓度的除草剂的杀伤曲线表明，方向和响应的幅度不同的除草剂，抗生素，和物种。当诱导时，五种不同类别的抗生素的MIC变化高达6倍。在某些情况下，MIC增加，而在其他情况下，它下降。除草剂浓度需要调用的最大响应高于目前的食品最大残留量，但在所有除草剂的应用水平。能够引起诱导的化合物在组合中具有累加效应。使用大肠杆菌的soxS-lacZ融合菌株在β-半乳糖苷酶测定中测试了AcrAB外排泵的诱导剂soxS的作用。麦草畏是sox调节子的中度诱导剂。用Phe-Arg β-萘酰胺（PAβN）（一种外排泵抑制剂）进行的生长试验证实，外排在存在麦草畏的情况下增加大肠杆菌对氯霉素的耐受性和存在草甘膦的情况下增加大肠杆菌对卡那霉素的耐受性中起着重要作用。与人类，家畜和重要昆虫的健康相关的接触途径进行了讨论。在农业、家庭花园和公共场所使用的越来越常见的化学品可以在潜在的病原体中诱导多重抗生素抗性表型。这种作用发生在同时暴露于抗生素时，并且比抗生素的致死作用更快。诱导反应的幅度可能会破坏抗生素治疗，并大大增加自发突变到更高水平的耐药性的可能性。在农场动物和重要昆虫（如蜜蜂）附近大量使用除草剂和抗生素，也可能损害其治疗效果，并推动抗生素的更多使用。为了解决抗生素耐药性危机，需要扩大我们对环境因素对耐药性演变的影响的看法。
Biocides, such as herbicides, are routinely tested for toxicity but not for sublethal effects on microbes. Many biocides are known to induce an adaptive multiple-antibiotic resistance phenotype. This can be due to either an increase in the expression of efflux pumps, a reduced synthesis of outer membrane porins, or both. Exposures of Escherichia coli and Salmonella enterica serovar Typhimurium to commercial formulations of three herbicides—dicamba (Kamba), 2,4-dichlorophenoxyacetic acid (2,4-D), and glyphosate (Roundup)—were found to induce a changed response to antibiotics. Killing curves in the presence and absence of sublethal herbicide concentrations showed that the directions and the magnitudes of responses varied by herbicide, antibiotic, and species. When induced, MICs of antibiotics of five different classes changed up to 6-fold. In some cases the MIC increased, and in others it decreased. Herbicide concentrations needed to invoke the maximal response were above current food maximum residue levels but within application levels for all herbicides. Compounds that could cause induction had additive effects in combination. The role of soxS, an inducer of the AcrAB efflux pump, was tested in β-galactosidase assays with soxS-lacZ fusion strains of E. coli. Dicamba was a moderate inducer of the sox regulon. Growth assays with Phe-Arg β-naphtylamide (PAβN), an efflux pump inhibitor, confirmed a significant role of efflux in the increased tolerance of E. coli to chloramphenicol in the presence of dicamba and to kanamycin in the presence of glyphosate. Pathways of exposure with relevance to the health of humans, domestic animals, and critical insects are discussed. Increasingly common chemicals used in agriculture, domestic gardens, and public places can induce a multiple-antibiotic resistance phenotype in potential pathogens. The effect occurs upon simultaneous exposure to antibiotics and is faster than the lethal effect of antibiotics. The magnitude of the induced response may undermine antibiotic therapy and substantially increase the probability of spontaneous mutation to higher levels of resistance. The combination of high use of both herbicides and antibiotics in proximity to farm animals and important insects, such as honeybees, might also compromise their therapeutic effects and drive greater use of antibiotics. To address the crisis of antibiotic resistance requires broadening our view of environmental contributors to the evolution of resistance.