摘要

       新的抗生素耐药基因（ARGs）在世界范围内的广泛分布和突然出现，决定了需要揭示哪些环境是其最重要的来源和宿主。ARGs与目前在人类病原体中发现的ARGs密切相关，发生在人类活动影响的环境中。然而，原始环境作为ARGs的起源和来源的作用，尤其是以海洋为代表的海洋环境，仍然没有得到充分的探讨和争议。在这里，由于海洋的性质，我们假设这种原始/低影响的海洋环境的抵抗力由遥远的ARG同源物表示。为了验证这一假设，我们对全球海洋取样（GOS）元基因组项目数据集进行了电子分析，重点是以金属β-内酰胺酶（MβLs）为ARG模型。MβLs水解碳青霉烯类药物是临床上最后的治疗选择之一，对公众健康构成了挑战。利用隐马尔可夫模型（HMM）轮廓，我们成功地识别了与B1、B2和B3亚类相关的MβL同源序列的高度多样性。它们大多分布于大西洋、印度洋和太平洋，与伊丽莎白菊属的MβL GOB染色体编码有关。仅观察到与获得的MβL酶（VIM、SPM-1和AIM-1）相关的亚基因组序列同源物数量减少，这些酶目前在临床上有影响。因此，低抗生素污染的海洋环境，如海洋，不太可能是对公众健康造成巨大威胁的ARGs的来源。

        The worldwide dispersion and sudden emergence of new antibiotic resistance genes (ARGs) determined the need in uncovering which environment participate most as their source and reservoir. ARGs closely related to those currently found in human pathogens occur in the resistome of anthropogenic impacted environments. However, the role of pristine environment as the origin and source of ARGs remains underexplored and controversy, particularly, the marine environments represented by the oceans. Here, due to the ocean nature, we hypothesized that the resistome of this pristine/low-impacted marine environment is represented by distant ARG homologs. To test this hypothesis we performed an in silico analysis on the Global Ocean Sampling (GOS) metagenomic project dataset focusing on the metallo-β-lactamases (MβLs) as the ARG model. MβLs have been a challenge to public health, since they hydrolyze the carbapenems, one of the last therapeutic choice in clinics. Using Hidden Markov Model (HMM) profiles, we were successful in identifying a high diversity of distant MβL homologs, related to the B1, B2, and B3 subclasses. The majority of them were distributed across the Atlantic, Indian, and Pacific Oceans being related to the chromosomally encoded MβL GOB present in Elizabethkingia genus. It was observed only a reduced number of metagenomic sequence homologs related to the acquired MβL enzymes (VIM, SPM-1, and AIM-1) that currently have impact in clinics. Therefore, low antibiotic impacted marine environment, as the ocean, are unlikely the source of ARGs that have been causing enormous threat to the public health.

        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895761/