College of Environment, Zhejiang University of Technology, Hangzhou 310032, P. R. China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou 310012, P. R. China.
Environ Sci Technol. 2023 May 23;57(20):7698-7708. doi: 10.1021/acs.est.3c01664. Epub 2023 May 10.
Antimicrobial peptides are a promising new class of antimicrobials that could address the antibiotic resistance crisis, which poses a major threat to human health. These peptides are present in all kingdoms of life, but especially in microorganisms, having multiple origins in diverse taxa. To date, there has been no global study on the diversity of antimicrobial peptides, the hosts in which these occur, and the potential for resistance to these agents. Here, we investigated the diversity and number of antimicrobial peptides in four main habitats (aquatic, terrestrial, human, and engineered) by analyzing 52,515 metagenome-assembled genomes. The number of antimicrobial peptides was higher in the human gut microbiome than in other habitats, and most hosts of antimicrobial peptides were habitat-specific. The relative abundance of genes that confer resistance to antimicrobial peptides varied between habitats and was generally low, except for the built environment and on human skin. The horizontal transfer of potential resistance genes among these habitats was probably constrained by ecological barriers. We systematically quantified the risk of each resistance determinant to human health and found that nearly half of them pose a threat, especially those that confer resistance to multiple AMPs and polymyxin B. Our results help identify the biosynthetic potential of antimicrobial peptides in the global microbiome, further identifying peptides with a low risk of developing resistance.
抗菌肽是一类有前景的新型抗菌药物，可解决抗生素耐药性危机，这对人类健康构成重大威胁。这些肽存在于所有生命领域，尤其是微生物中，在不同的分类群中具有多种起源。迄今为止，尚未有关于抗菌肽的多样性、这些肽的宿主以及对这些药物产生耐药性的潜力的全球研究。在这里，我们通过分析 52515 个宏基因组组装基因组，研究了四大主要栖息地（水生、陆地、人类和工程）中抗菌肽的多样性和数量。抗菌肽在人类肠道微生物组中的数量高于其他栖息地，并且大多数抗菌肽的宿主都是特定栖息地的。对抗菌肽产生抗性的基因的相对丰度在不同栖息地之间有所不同，除了人造环境和人体皮肤外，通常较低。这些栖息地之间潜在抗性基因的水平转移可能受到生态障碍的限制。我们系统地量化了每个抗性决定因素对人类健康的风险，发现近一半的抗性决定因素构成威胁，特别是那些对多种 AMP 和多粘菌素 B 产生抗性的决定因素。我们的研究结果有助于确定全球微生物组中抗菌肽的生物合成潜力，进一步确定具有低耐药风险的肽。
