Proximity-ligation metagenomics reveals differential plasmid and chromosomal antimicrobial resistance gene carriage in disrupted gut ecosystems.

Distinct ecological pressures shape accumulation of antimicrobial resistance genes (ARGs) and virulence genes in the gut microbiome. In this study, we used proximity ligation shotgun metagenomics to characterize bacterial host-mobilome relationships associated with antimicrobial resistance and virulence genes in two disease cohorts with microbiome dysbiosis: recurrent Clostridioides difficile infection (rCDI) and cirrhosis. Microbiome dysbiosis in patients with rCDI is primarily driven by prolonged antibiotic exposure, whereas dysbiosis in patients with cirrhosis results from altered gut physiology. We found an increased relative abundance of chromosomally linked antibiotic resistance determinants in both disease cohorts compared with healthy controls. The rCDI cohorts additionally exhibited increased relative abundance of plasmid-mediated ARGs.