Gut Microbiome Perturbation Affected Conjugative Transfer of Antimicrobial Resistance Genes

Abstract

The global spread of antimicrobial resistance genes (ARGs) poses a significant threat to public health. While antibiotics effectively treat bacterial infections, they can also induce gut dysbiosis, the severity of which varies depending on the specific antibiotic treatment used. However, it remains unclear how gut dysbiosis affects the mobility and dynamics of ARGs. To address this, mice were pre-treated with streptomycin, ampicillin, or sulfamethazine, and then orally inoculated withSalmonella entericaserovar Typhimurium andS. Heidelberg carrying a multi-drug resistance IncA/C plasmid. The streptomycin pre- treatment caused severe microbiome perturbation, promoting high-density colonization ofS. Heidelberg andS. Typhimurium, and enabling IncA/C transfer fromS. Heidelberg toS. Typhimurium and a commensalEscherichia coli. The ampicillin pre-treatment induced moderate microbiome perturbation, supporting onlyS. Heidelberg colonization and IncA/C transfer to commensalE. coli. The sulfamethazine pre-treatment led to mild microbiome perturbation, favoring neitherSalmonella spp. colonization nor conjugative plasmid transfer. The degree of gut dysbiosis also influenced the enrichment or depletion of ARGs associated with mobile plasmids or core commensal bacteria, respectively. These findings underscore the significance of pre-existing gut dysbiosis induced by various antibiotic treatments on ARG dissemination and may inform prudent antibiotic use practices.