Eco-Geography Reverses Dominant AMR Reservoirs in Klebsiella pneumoniae: Integron-Rich Mobilomes and Cross-Niche Connectivity.

Multidrug-resistant Klebsiella pneumoniae is a global health threat circulating across humans, animals, food, and environments. Despite increasing One Health surveillance, it remains unclear whether the dominant antimicrobial resistance (AMR) reservoirs in K. pneumoniae are universal or depend on regional ecological context. Here, a synchronized One Health survey in Pingguo, China (5384 samples) is integrated with parallel cross-niche datasets (Italy, Ghana) and a 69184 public genome collection, mapping AMR ecology via network metrics and lineage-aware mixed models. In Pingguo, high-risk determinants are enriched in humans, whereas overall AMR burdens and multidrug resistance platforms are enriched outside humans. Across the public dataset, AMR reservoir dominance varies eco-geographically, with nonhuman isolates carrying higher AMR gene burdens in the China subset (mean +4.5 per isolate), largely due to animal and environmental isolates, while human isolates carry higher burdens in the U.S. and Europe subsets. Lineage explains 44.8% of the burden difference. Remaining within-lineage differences, reservoir-matched integron enrichment, and region-specific connectivity suggest additional horizontal gene transfer-related contributions. This is supported in Pingguo by a highly structured cross-niche plasmid-sharing network shaped by specific plasmid groups and successful lineages. Overall, dominant AMR reservoirs are eco-geographically contingent. Integron load and cross-niche connectivity provide indicators for tiered, region-tailored surveillance.