Prophages as a source of antimicrobial resistance genes in the human microbiome

Abstract

Prophages--viruses that integrate into bacterial genomes--are ubiquitous in the microbial realm. Prophages contribute significantly to horizontal gene transfer, including the potential spread of antimicrobial resistance (AMR) genes, because they can collect host genes. Understanding their role in the human microbiome is essential for fully understanding AMR dynamics and possible clinical implications. We analysed almost 15,000 bacterial genomes for prophages and AMR genes. The bacteria were isolated from diverse human body sites and geographical regions, and their genomes were retrieved from GenBank. AMR genes were detected in 6.6% of bacterial genomes, with a higher prevalence in people with symptomatic diseases. We found a wide variety of AMR genes combating multiple drug classes. We discovered AMR genes previously associated with plasmids, such as blaOXA-23 in Acinetobacter baumannii prophages or genes found in prophages in species they had not been previously described in, such as mefA-msrD in Gardnerella prophages, suggesting prophage-mediated gene transfer of AMR genes. Prophages encoding AMR genes were found at varying frequencies across body sites and geographical regions, with Asia showing the highest diversity of AMR genes. ImportanceAntimicrobial resistance (AMR) is a growing threat to public health, and understanding how resistance genes spread between bacteria is essential for controlling their dissemination. Bacteriophages, viruses that infect bacteria, have been recognised as potential vehicles for transferring these resistance genes, but their role in the human microbiome remains poorly understood. We examined nearly 15,000 bacterial genomes from various human body sites and regions worldwide to investigate how often prophages carry AMR genes in the human microbiome. Although AMR genes were uncommon in prophages, we identified diverse resistance genes across multiple bacterial species and drug classes, including some typically associated with plasmids. These findings reveal that prophages may contribute to the spread of resistance genes, highlighting an overlooked mechanism in the dynamics of AMR transmission. Ongoing monitoring of prophages is critical to fully understanding the pathways through which resistance genes move within microbial communities and impact human health.