摘要

抗生素和金属的复杂混合物存在于许多环境中，从城市污水到灌溉水和用作农业肥料的粪肥。这种药物和金属的混合物对局部细菌群落施加独特的选择压力，并且可以作为富集抗生素抗性基因的热点。以前，环境中金属的存在与抗生素耐受性的增加有关。在这项研究中，我们研究了抗生素抗性沙门氏菌菌株的金属增强选择。与三种不同的抗生素组合检查六种环境相关金属。通过在每种金属 - 抗生素组合中进行抗生素抗性突变体和同基因野生型之间的竞争，我们评估了抗生素对抗性菌株的最小选择性浓度（MSC）。金属银，镉和汞都表现出增强作用，与没有金属的情况相比，抗生素的MSC减少了5倍。我们进一步表明，增强金属增加了细胞外膜的渗透性。这些结果表明，金属的存在可降低选择抗生素抗性菌株所需的抗生素浓度，并且它们表明该过程涉及在外膜损伤后金属促进的抗生素摄取。

Complex mixtures of antibiotics and metals are present in many environments ranging from municipal sewage to irrigation water and manure used as agricultural fertilizer. Such mixtures of drugs and metals exert unique selection pressures on local bacterial communities and could function as hotspots for enrichment of antibiotic resistance genes. The presence of metals in the environment has previously been linked to increases in tolerance to antibiotics. In this study, we investigated metal-potentiated selection of antibiotic resistant Salmonella enterica strains. Six environmentally relevant metals were examined in combinations with three different antibiotics. By performing competitions between an antibiotic resistant mutant and the isogenic wild type in each metal-antibiotic combination, we assessed the minimal selective concentration (MSC) of the antibiotic for the resistant strain. The metals silver, cadmium and mercury all exhibited potentiating effects, reducing the MSC of the antibiotic up to 5-fold as compared to in the absence of the metal. We further show that the potentiating metals increased permeability of the cellular outer membrane. These results demonstrate that the presence of a metal can decrease the concentration of an antibiotic required to select for an antibiotic resistant strain, and they indicate that this process involves metal-facilitated uptake of the antibiotic following damage to the outer membrane.

http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1237647&dswid=-8233