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Selection for Resistance to a Glyphosate-Containing Herbicide in Salmonella enterica Does Not Result in a Sustained Activation of the Tolerance Response or Increased Cross-Tolerance and Cross-Resistance to Clinically Important Antibiotics
Applied and Environmental Microbiology ( IF 4.4 ) Pub Date : 2020-11-24 , DOI: 10.1128/aem.01204-20
Judith Pöppe 1 , Katrin Bote 1 , Abhinaya Ramesh 1 , Jayaseelan Murugaiyan 1, 2 , Benno Kuropka 3 , Michael Kühl 1 , Paul Johnston 4, 5, 6 , Uwe Roesler 1 , Olga Makarova 1
Affiliation  

Evolution of bacterial tolerance to antimicrobials precedes evolution of resistance and may result in cross-tolerance, cross-resistance, or collateral sensitivity to other antibiotics. Transient exposure of gut bacteria to glyphosate, the world’s most widely used herbicide, has been linked to the activation of the stress response and changes in susceptibility to antibiotics. In this study, we investigated whether chronic exposure to a glyphosate-based herbicide (GBH) results in resistance, a constitutive activation of the tolerance and stress responses, and cross-tolerance or cross-resistance to antibiotics. Of the 10 farm animal-derived clinical isolates of Salmonella enterica subjected to experimental evolution in increasing concentrations of GBH, three isolates showed stable resistance with mutations associated with the glyphosate target gene aroA and no fitness costs. Global quantitative proteomics analysis demonstrated activation of the cellular tolerance and stress response during the transient exposure to GBH but not constitutively in the resistant mutants. Resistant mutants displayed no cross-resistance or cross-tolerance to antibiotics. These results suggest that while transient exposure to GBH triggers cellular tolerance response in Salmonella enterica, this response does not become genetically fixed after selection for resistance to GBH and does not result in increased cross-tolerance or cross-resistance to clinically important antibiotics under our experimental conditions.

中文翻译:

在肠沙门氏菌中选择对草甘膦除草剂的抗性不会导致对临床重要抗生素的耐受性反应持续激活或交叉耐受性和交叉耐药性增加

细菌对抗菌素的耐受性的演变先于耐药性的发展,并可能导致对其他抗生素的交叉耐受性,交叉耐药性或附带敏感性。肠道细菌短暂接触草甘膦(世界上使用最广泛的除草剂)与激活应激反应和改变对抗生素的敏感性有关。在这项研究中,我们调查了长期暴露于草甘膦基除草剂(GBH)是否会导致耐药性,耐受性和应激反应的组成型激活以及对抗生素的交叉耐受性或交叉耐药性。在10种农场动物来源的沙门氏菌临床分离株中在不断增加的GBH浓度下进行了实验性进化后,三个分离株表现出稳定的抗药性,并且具有与草甘膦目标基因aroA相关的突变,并且没有使用成本。全球定量蛋白质组学分析表明,在短暂暴露于GBH的过程中激活了细胞耐受性和应激反应,但在抗性突变体中不是组成型的。抗性突变体对抗生素没有交叉耐药性或交叉耐受性。这些结果表明,短暂暴露于GBH会触发肠沙门氏菌的细胞耐受反应,在选择对GBH的耐药性后,这种反应不会在遗传上固定下来,并且在我们的实验条件下不会导致对临床上重要的抗生素的交叉耐受性或交叉耐药性增加。
更新日期:2020-11-25
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