Spatially and Temporally Confined Response of Gastrointestinal Antibiotic Resistance Gene Levels to Sulfadiazine and Extracellular Antibiotic Resistance Gene Exposure in Mice

Abstract

This work aims to investigate the impact of antibiotics and extracellular antibiotic resistance genes (eARGs) on the dynamics of gastrointestinal antimicrobial resistance (AMR). The antibiotic resistance gene (ARG) levels of different segments of the gastrointestinal tract of mouse models were analyzed and compared after exposure to clinical concentrations of sulfadiazine and environmental levels of eARGs carried by the conjugative plasmid pR55. Exposure to sulfadiazine and eARGs led to significant changes in ARG levels by as many as four log-folds. Further analysis showed that the response of ARG levels appeared from 12-16 days after exposure and diminished 20 days after exposure. The responses in ARG levels were also restricted to different gastrointestinal segments for sulfadiazine and eARGs. Combined exposure of sulfadiazine and eARGs was unable to further increase ARG levels. From these findings, we concluded that the short-term consumption of environmental levels of eARGs and uptake of clinical levels of antibiotics lead to a spatially and temporally confined response in gastrointestinal AMR. These findings further clarify the detrimental impacts of antibiotic and eARG uptake, and the complexity of AMR development and dissemination dynamics in the gastrointestinal tract.