Background Following the ban on antimicrobial usage for growth promotion in animal husbandry in the EU, non-antimicrobial agents including heavy metal ions (e.g. zinc and copper), prebiotics or probiotics have been suggested as alternatives. Zinc has extensively been used in pig farming, particularly during weaning of piglets to improve animal health and growth rates. Recent studies, however, have suggested that high dietary zinc feeding during weaning of piglets increases the proportion of multi-drug resistant E. coli in the gut, contraindicating the appropriateness of zinc as an alternative. The underlying mechanisms of zinc effects on resistant bacteria remains unclear, but co-selection processes could be involved. In this study, we determined whether E. coli isolates from intestinal contents of piglets that had been supplemented with high concentrations of zinc acquired a higher tolerance towards zinc, and whether multi-drug resistant isolates tolerated higher zinc concentrations. In addition, we compared phenotypic zinc and copper resistance of E. coli isolates for possible correlation between phenotypic resistance/tolerance to different bivalent ionic metals. Results We screened phenotypic zinc/copper tolerance of 210 isolates (including antimicrobial resistant, multi-drug resistant, and non-resistant E. coli) selected from two, independent zinc-feeding animal trials by determining a zinc/copper minimal inhibitory concentration (Merlin, Bornheim-Hersel, Germany). In both trials, groups of piglets were supplemented either with high dietary zinc (> 2000 ppm) or control (50-70 ppm, background) concentrations. Our observations showed that high concentration zinc exposure did not have an effect on either zinc or copper phenotypic tolerance of E. coli isolates from the animals. No significant association was found between antimicrobial resistance and phenotypic zinc/copper tolerance of the same isolates. Conclusion Our findings argue against a co-selection mechanism of antimicrobial drug-resistance and zinc tolerance after dietary zinc supplementation in weaning piglets. An explanation for an increase in multi-drug resistant isolates from piglets with high zinc dietary feeding could be that resistant bacteria to antimicrobial agents are more persistent to stresses such as zinc or copper exposure.

中文翻译：

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仔猪粪便大肠杆菌分离株中的表型锌耐药性与多重耐药性无关。

背景 随着欧盟禁止在畜牧业中使用抗菌素促进生长，包括重金属离子（如锌和铜）、益生元或益生菌在内的非抗菌剂已被建议作为替代品。锌已广泛用于养猪业，特别是在仔猪断奶期间以改善动物健康和生长速度。然而，最近的研究表明，在仔猪断奶期间高饲喂锌会增加肠道中耐多药大肠杆菌的比例，从而禁止使用锌作为替代品。锌对耐药菌影响的潜在机制仍不清楚，但可能涉及共选择过程。在本研究中，我们确定 E. 从补充高浓度锌的仔猪肠道内容物中分离出的大肠杆菌对锌具有更高的耐受性，以及多重耐药菌株是否耐受更高的锌浓度。此外，我们比较了大肠杆菌分离株的表型锌和铜抗性，以了解表型抗性/耐受性与不同二价离子金属的可能相关性。结果 我们通过确定锌/铜最小抑制浓度（Merlin ，博恩海姆-赫塞尔，德国）。在这两项试验中，仔猪组补充了高膳食锌（> 2000 ppm）或对照（50-70 ppm，背景）浓度。我们的观察表明，高浓度锌暴露对动物大肠杆菌分离株的锌或铜表型耐受性没有影响。在相同分离株的抗菌素耐药性和表型锌/铜耐受性之间没有发现显着关联。结论 我们的研究结果反驳了断奶仔猪日粮补锌后抗菌药物耐药性和锌耐受性的共同选择机制。从高锌日粮喂养的仔猪身上分离出多药耐药菌株增加的一个解释可能是，对抗菌剂产生耐药性的细菌对锌或铜暴露等压力更持久。我们的观察表明，高浓度锌暴露对动物大肠杆菌分离株的锌或铜表型耐受性没有影响。在相同分离株的抗菌素耐药性和表型锌/铜耐受性之间没有发现显着关联。结论 我们的研究结果反驳了断奶仔猪日粮补锌后抗菌药物耐药性和锌耐受性的共同选择机制。从高锌日粮喂养的仔猪身上分离出多药耐药菌株增加的一个解释可能是，对抗菌剂产生耐药性的细菌对锌或铜暴露等压力更持久。我们的观察表明，高浓度锌暴露对动物大肠杆菌分离株的锌或铜表型耐受性没有影响。在相同分离株的抗菌素耐药性和表型锌/铜耐受性之间没有发现显着关联。结论 我们的研究结果反驳了断奶仔猪日粮补锌后抗菌药物耐药性和锌耐受性的共同选择机制。从高锌日粮喂养的仔猪身上分离出多药耐药菌株增加的一个解释可能是，对抗菌剂产生耐药性的细菌对锌或铜暴露等压力更持久。在相同分离株的抗菌素耐药性和表型锌/铜耐受性之间没有发现显着关联。结论 我们的研究结果反驳了断奶仔猪日粮补锌后抗菌药物耐药性和锌耐受性的共同选择机制。从高锌日粮喂养的仔猪身上分离出多药耐药菌株增加的一个解释可能是，对抗菌剂产生耐药性的细菌对锌或铜暴露等压力更持久。在相同分离株的抗菌素耐药性和表型锌/铜耐受性之间没有发现显着关联。结论 我们的研究结果反驳了断奶仔猪日粮补锌后抗菌药物耐药性和锌耐受性的共同选择机制。从高锌日粮喂养的仔猪身上分离出多药耐药菌株增加的一个解释可能是，对抗菌剂产生耐药性的细菌对锌或铜暴露等压力更持久。