摘要

当生物体受到环境挑战时，包括生长抑制剂和毒素，进化经常选择内源基因的重复，其过度表达可以提供选择性优势。这种事件既发生在自然环境中，也发生在临床环境中。微生物细胞（它们的人口众多，生成时间短）经常对一系列抗菌剂产生抗性。虽然微生物对抗生素药物的耐药性已有文献报道，但对金属毒性抵抗的遗传因素的关注不多。为了评估哪些过表达的基因可赋予革兰氏阴性细菌对金属毒性的抗性，我们将过量表达所有大肠杆菌可读框（ORF）的质粒转化为幼稚细胞，并选择存活于有毒浓度的六种过渡金属中： Cd，Co，Cu，Ni，Ag，Zn。这些选择确定了48次点击。在这些命中的每一个中，内源性大肠杆菌基因的过表达在存在至少一种有毒金属时提供了选择性优势。令人惊讶的是，大多数这些病例（28/48）以前并不知道在金属抵抗或体内平衡中起作用。这些研究结果突出了生物系统可以部署以适应含有毒性浓度的金属环境的多种机制。

When organisms are subjected to environmental challenges, including growth inhibitors and toxins, evolution often selects for the duplication of endogenous genes, whose overexpression can provide a selective advantage. Such events occur both in natural environments and in clinical settings. Microbial cells—with their large populations and short generation times—frequently evolve resistance to a range of antimicrobials. While microbial resistance to antibiotic drugs is well documented, less attention has been given to the genetic elements responsible for resistance to metal toxicity. To assess which overexpressed genes can endow gram-negative bacteria with resistance to metal toxicity, we transformed a collection of plasmids overexpressing all E. coli open reading frames (ORFs) into naive cells, and selected for survival in toxic concentrations of six transition metals: Cd, Co, Cu, Ni, Ag, Zn. These selections identified 48 hits. In each of these hits, the overexpression of an endogenous E. coligene provided a selective advantage in the presence of at least one of the toxic metals. Surprisingly, the majority of these cases (28/48) were not previously known to function in metal resistance or homeostasis. These findings highlight the diverse mechanisms that biological systems can deploy to adapt to environments containing toxic concentrations of metals.

https://link.springer.com/article/10.1007/s00239-018-9830-3