摘要

人类活动负责在医疗保健和农业环境中积累金属，质粒编码的金属耐受操纵子使细菌能够在这种条件下迅速适应金属暴露。虽然已经描述了许多金属抗性系统的作用机制，但是对它们在含金属环境中共同选择抗生素抗性中的作用的理解仍然有限。质粒编码的金属抗性基因是否赋予显着的选择性优势是令人感兴趣的，因为它对质粒富集和质粒携带的抗生素抗性基因的扩散具有意义。为了增加我们对质粒介导的金属抗性的理解，我们研究了在没有和存在银和铜的情况下生长期间大肠杆菌中的sil操纵子及其表型。我们发现sil操纵子对银和铜都有抵抗力。然而，它仅由铜诱导，并且由双组分silS基因中的点突变引起的组成型表达提供高水平的银抗性。此外，我们发现高银抗性突变体可以在银的存在下富集。这种富集需要共同选择多药抗性质粒pUUH239.2。我们的结果表明，铜抗性操纵子可以在单点突变后提供高水平的银抗性，并且银抗性表型随后可以在银的存在下共同选择抗生素抗性。

Human activities are responsible for an accumulation of metals in health care and agricultural environments, and plasmid-encoded metal tolerance operons enable bacteria to rapidly adapt to metal exposure under such conditions. While the mechanisms of action of many metal resistance systems have been described, there is still limited understanding of their role in co-selection of antibiotic resistance in metal-containing environments. Whether plasmid-encoded metal resistance genes confer significant selective advantages is of interest as it has implications for plasmid enrichment and the spread of plasmid-borne antibiotic resistance genes. To increase our understanding of plasmid-mediated metal resistance, we studied the sil operon and its phenotypes in E. coli during growth in the absence and presence of silver and copper. We found that the sil operon provides resistance to both silver and copper. However, it is induced by copper only, and constitutive expression due to point mutations in the two-component silS gene provides high-level silver resistance. Furthermore, we showed that a high-level silver resistant mutant could be enriched in the presence of silver. This enrichment entailed co-selection of the multidrug resistance plasmid pUUH239.2. Our results show that a copper resistance operon can provide high-level silver resistance following a single point mutation, and that the silver resistance phenotype subsequently can co-select for antibiotic resistance in the presence of silver. 

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