Anthropogenic land use exerts selection pressures on the resistome of a wild rodent

Antimicrobial resistance poses a significant global health challenge. However, the factors maintaining antimicrobial resistance genes (ARGs) in wildlife microbiomes remain unclear particularly in species inhabiting human-dominated landscapes. We analysed 875 gut metagenomes from wild house mice (Mus musculus) on German farms between 2016 and 2022 to identify environmental and host determinants of ARG occurrence. Using joint species distribution models, we quantified the influence of landscape, climate and mouse associated characteristics on the occurrence of individual ARGs and on trait dependence among genes. Environmental variables and livestock farming intensity explained more than 21% of ARG variation, whereas host characteristics accounted for less than 10%. Analysis of ARG traits revealed that agricultural land use and exposure to livestock increased the occurrence of mobile ARGs. Pig density was strongly associated with integron-encoded sulfonamide resistance genes and genes conferring tetracycline and beta-lactam resistance. Consistent with these findings, mouse resistomes closely resembled those of livestock manure. Taken together, our results show that landscape conditions, particularly farming intensity, shape the distribution of specific ARGs and mobile ARGs in house mice microbiomes. Understanding the factors impacting ARGs prevalence in wildlife is crucial for determining transmission of antimicrobial resistant microorganisms from animal and environmental reservoirs.