Antimicrobial resistance genes (ARGs) have rapidly emerged and spread
globally, but the pathways driving their spread remain poorly understood. We
analyzed 1240 sewage samples from 351 cities across 111 countries, comparing
ARGs known to be mobilized with those identified through functional meta-
genomics (FG). FG ARGs showed stronger associations with bacterial taxa than
the acquired ARGs. Network analyses further confirmed this and showed
potential for source attribution of both known and novel ARGs. The FG
resistome was more evenly dispersed globally, whereas the acquired resistome
followed distinct geographical patterns. City-wise distance-decay analyses
revealed that the FG ARGs showed significant decay within countries but not
across regions or globally. In contrast, acquired ARGs showed decay at both
national and regional scales. At the variant level, both ARG groups had sig-
nificant national and regional distance-decay effects, but only FG ARGs at a
global scale. Additionally, we observed stronger distance effects in Sub-
Saharan Africa and East Asia compared to North America. Our findings suggest
that differential selection and niche competition, rather than dispersal, shape
the global resistome patterns. A limited number of bacterial taxa may act as
reservoirs of latent FG ARGs, highlighting the need of targeted surveillance to
mitigate future resistance threats.