The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet Bygning 220, 2800 Kgs. Lyngby, Denmark.
Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Nat Commun. 2017 Jun 7;8:15784. doi: 10.1038/ncomms15784.
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.
据推测，一些在致病菌中发现的抗生素耐药基因（ARGs）来自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。我们在变形菌门中发现了一些基因，包括一些病原体，这些基因似乎与已知对抗生素具有抗药性的放线菌 ARGs 密切相关，这些抗生素对临床非常重要。此外，我们还发现了两个放线菌 ARG 最近水平转移到变形菌病原体的潜在例子。基于这些生物信息学证据，我们提出并实验验证了一个“携带回”的转移机制，涉及到从变形菌到放线菌的载体序列的共轭转移，载体序列与放线菌 ARG 的重组，然后是携带载体的 ARG 的自然转化。我们的研究结果支持了 ARGs 从产生抗生素的放线菌到变形菌的古老和（可能）最近的转移的存在，并为一个明确的机制提供了证据。
