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

SIMPLE SUMMARY: The emergence of bacterial resistance to antibiotics is a significant threat to human health, because it makes controlling bacterial infection more difficult. Antibiotic resistance genes that can cause bacteria to resist antibiotics are ubiquitous in the environment and consumed daily by humans via food and water. It has long been suspected that uptake of these genes may lead to increased antibiotic resistance in bacteria that colonize human bodies, which in turn may lead to infections that are hard to cure. In addition, the uptake of antibiotics may also lead to an increase in antibiotic resistance, resulting in negative impacts for further treatment. To address these concerns, we applied an in vivo study to determine how the antibiotic resistance levels in the gastrointestinal tracts of mice models react to uptake of antibiotics and antibiotic resistance genes. With quantitative analysis, both antibiotics and antibiotic resistance genes were found to indeed increase antibiotic resistance levels. However, this response was found to be both temporally and spatially confined: they are acute responses that only occur 12–16 days after exposure, and they only occur in certain segments of the gastrointestinal tract. This work further suggests caution over antibiotic resistance gene pollution and antibiotic misuse. 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.