Antimicrobial Peptides in the Global Microbiome: Biosynthetic Genes and Resistance Determinants

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.