摘要

    抗生素抗性通过抗生素抗性基因（ARG）的水平转移在细菌之间传播。在这里，我们着手确定细菌进化枝中ARG转移的预测特征。我们使用统计框架来确定推定的水平转移的ARG以及传播它们的细菌群。我们确定了152个包含22,963个细菌基因组的基因交换网络。对ARG周围序列的分析确定了编码假定的动员元件（例如转座酶和整合）的基因，这些基因可能参与基因组之间的基因转移。某些ARGs似乎经常被不同的移动遗传元件所动员。我们表征这些动员元素的系统发育范围，以预测已知的ARGs的潜在未来传播。使用来自链球菌科，葡萄球菌科和肠杆菌科的472,798个基因组的单独数据库，我们确认了94个预测的动员中的34个。我们探索了动员之外的转移障碍，并通过实验证明了宿主的生理限制可以解释为什么特定基因在很大程度上局限于革兰氏阴性细菌，尽管它们的移动元件支持向革兰氏阳性细菌的传播。我们的方法可能潜在地实现对未来抗性基因传播的更好的风险评估。

    Antibiotic resistance spreads among bacteria through horizontal transfer of antibiotic resistance genes (ARGs). Here, we set out to determine predictive features of ARG transfer among bacterial clades. We use a statistical framework to identify putative horizontally transferred ARGs and the groups of bacteria that disseminate them. We identify 152 gene exchange networks containing 22,963 bacterial genomes. Analysis of ARG-surrounding sequences identify genes encoding putative mobilisation elements such as transposases and integrases that may be involved in gene transfer between genomes. Certain ARGs appear to be frequently mobilised by different mobile genetic elements. We characterise the phylogenetic reach of these mobilisation elements to predict the potential future dissemination of known ARGs. Using a separate database with 472,798 genomes from Streptococcaceae, Staphylococcaceae and Enterobacteriaceae, we confirm 34 of 94 predicted mobilisations. We explore transfer barriers beyond mobilisation and show experimentally that physiological constraints of the host can explain why specific genes are largely confined to Gram-negative bacteria although their mobile elements support dissemination to Gram-positive bacteria. Our approach may potentially enable better risk assessment of future resistance gene dissemination.

    https://www.nature.com/articles/s41467-021-22757-1