摘要

抗生素抗性基因（ARG）在肠道微生物群中普遍存在，但仍不清楚ARG转移的频率，特别是病原体。传统上，ARG传播归因于通过DNA转化，细菌缀合或广义转导介导的水平转移。然而，最近的病毒宏基因组（virome）分析表明ARG经常由噬菌体携带，这与传统观点不同，即噬菌体基因组很少编码ARG。在这里，我们使用文献中探索性和保守性的生物信息学策略来检测噬菌体基因组中的ARG，并通过实验评估使用探索性阈值预测的ARG子集。由于相似性较低且与抗生素抗性无关的蛋白质匹配，使用探索性阈值（421预测值与已知的2种已知值）极大地高估了1181噬菌体基因组中的ARG丰度。与此一致的是，使用探索性阈值预测的四个ARG经实验评估并未能在大肠杆菌中赋予抗生素抗性。对可用的人或小鼠相关病毒的ARG及其基因组背景的再分析表明，真正的ARG归因于病毒中的噬菌体先前被高估了。这些发现为病毒中ARG的记录提供了指导，并重申ARG很少在噬菌体中编码。

Antibiotic resistance genes (ARGs) are pervasive in gut microbiota, but it remains unclear how often ARGs are transferred, particularly to pathogens. Traditionally, ARG spread is attributed to horizontal transfer mediated either by DNA transformation, bacterial conjugation or generalized transduction. However, recent viral metagenome (virome) analyses suggest that ARGs are frequently carried by phages, which is inconsistent with the traditional view that phage genomes rarely encode ARGs. Here we used exploratory and conservative bioinformatic strategies found in the literature to detect ARGs in phage genomes, and experimentally assessed a subset of ARG predicted using exploratory thresholds. ARG abundances in 1181 phage genomes were vastly overestimated using exploratory thresholds (421 predicted vs 2 known), due to low similarities and matches to protein unrelated to antibiotic resistance. Consistent with this, four ARGs predicted using exploratory thresholds were experimentally evaluated and failed to confer antibiotic resistance in Escherichia coli. Reanalysis of available human- or mouse-associated viromes for ARGs and their genomic context suggested thatbona fide ARG attributed to phages in viromes were previously overestimated. These findings provide guidance for documentation of ARG in viromes, and reassert that ARGs are rarely encoded in phages.

https://www.nature.com/articles/ismej201690