摘要

据推测，在致病细菌中发现的一些抗生素抗性基因（ARG）来源于产生抗生素的放线菌。在这里，我们提供了支持这一假设的生物信息学和实验证据。我们确定变形杆菌中的基因，包括一些病原体，这些基因似乎与已知赋予对临床重要抗生素的抗性的放线菌ARG密切相关。此外，我们确定了最近将放线菌ARG水平转移至变形杆菌病原体的两个潜在实例。基于这种生物信息学证据，我们提出并实验性地测试了转移的“回传”机制，涉及载体序列从变形杆菌到放线菌的共轭转移，载体序列与放线菌ARG的重组，然后自然转化变形杆菌与运营商夹心的ARG。我们的研究结果支持ARGs从抗生素产生的放线菌到变形杆菌的古老和可能最近的转移的存在，并为确定的机制提供证据。

It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify genes in proteobacteria, including some pathogens, that appear to be closely related to actinobacterial ARGs known to confer resistance against clinically important antibiotics. Furthermore, we identify two potential examples of recent horizontal transfer of actinobacterial ARGs to proteobacterial pathogens. Based on this bioinformatic evidence, we propose and experimentally test a ‘carry-back’ mechanism for the transfer, involving conjugative transfer of a carrier sequence from proteobacteria to actinobacteria, recombination of the carrier sequence with the actinobacterial ARG, followed by natural transformation of proteobacteria with the carrier-sandwiched ARG. Our results support the existence of ancient and, possibly, recent transfers of ARGs from antibiotic-producing actinobacteria to proteobacteria, and provide evidence for a defined mechanism.

https://www.nature.com/articles/ncomms15784