摘要
出身背景
人类、动物和外部环境中的细菌群落保持着大量的抗生素耐药性基因（ARGs）。然而，这些ARG很少有很好的特征，因此在现有的抗性基因数据库中建立。相比之下，在大多数基于测序的研究中，剩余的潜在ARG通常是未知的和被忽视的。因此，我们对耐药性及其多样性的看法是不完整的，这阻碍了我们评估尚未发现的耐药性决定因素的推广和传播风险的能力。
后果
创建了一个由已建立和潜在的ARG（当前抗性基因库中不存在的ARG）组成的参考数据库。通过分析10000多个宏基因组样本，我们发现在所有研究环境中，包括人类和动物相关的微生物群中，潜在的ARG比已建立的ARG更丰富和多样。泛抗性体，即存在于环境中的所有ARG，在很大程度上由潜在的ARG主导。相比之下，核心耐药性，即常见的ARG，包括潜在的和已建立的ARG。我们确定了环境之间共享和/或存在于人类病原体中的几种潜在ARG。对这些基因的上下文分析表明，它们位于可移动的遗传元件上，包括结合元件。此外，我们发现废水微生物群具有惊人的大的泛核心耐药性，这使其成为动员和促进潜在ARGs的潜在高风险环境。
结论
我们的研究结果表明，潜在的ARGs普遍存在于所有环境中，并构成了一个多样化的库，可以从中招募新的抗性决定因素来对抗病原体。一些潜在的ARG已经具有很高的移动潜力，并且存在于人类病原体中，这表明它们可能对人类健康构成新的威胁。我们的结论是，需要考虑包括潜在和已建立ARGs在内的完全耐药性，以正确评估与抗生素选择压力相关的风险。
Abstract
Background
Bacterial communities in humans, animals, and the external environment maintain a large collection of antibiotic resistance genes (ARGs). However, few of these ARGs are well-characterized and thus established in existing resistance gene databases. In contrast, the remaining latent ARGs are typically unknown and overlooked in most sequencing-based studies. Our view of the resistome and its diversity is therefore incomplete, which hampers our ability to assess risk for promotion and spread of yet undiscovered resistance determinants.

Results
A reference database consisting of both established and latent ARGs (ARGs not present in current resistance gene repositories) was created. By analyzing more than 10,000 metagenomic samples, we showed that latent ARGs were more abundant and diverse than established ARGs in all studied environments, including the human- and animal-associated microbiomes. The pan-resistomes, i.e., all ARGs present in an environment, were heavily dominated by latent ARGs. In comparison, the core-resistome, i.e., ARGs that were commonly encountered, comprised both latent and established ARGs. We identified several latent ARGs shared between environments and/or present in human pathogens. Context analysis of these genes showed that they were located on mobile genetic elements, including conjugative elements. We, furthermore, identified that wastewater microbiomes had a surprisingly large pan- and core-resistome, which makes it a potentially high-risk environment for the mobilization and promotion of latent ARGs.

Conclusions
Our results show that latent ARGs are ubiquitously present in all environments and constitute a diverse reservoir from which new resistance determinants can be recruited to pathogens. Several latent ARGs already had high mobile potential and were present in human pathogens, suggesting that they may constitute emerging threats to human health. We conclude that the full resistome—including both latent and established ARGs—needs to be considered to properly assess the risks associated with antibiotic selection pressures.

https://link.springer.com/article/10.1186/s40168-023-01479-0