Lineage-Specific Associations between the Resistome and Mobilome across 10,500 Globally Distributed Acinetobacter...

Background: Acinetobacter baumannii is a major nosocomial pathogen with extensive antimicrobial resistance, yet the extent to which resistome burden covaries with mobilome architecture across clonal backgrounds remains unclear at the global scale. Using a curated dataset of 10,500 high-quality genomes, this study examined lineage-resolved relationships among AMRFinder-detected resistance determinants, insertion sequence (IS) burden, plasmid diversity, predicted plasmid mobility, and virulence-associated gene presence. Results: The population structure was highly uneven and dominated by a small number of lineages. Using total AMRFinder burden, genome-level associations with IS burden and plasmid replicon diversity were modest (Spearman rho = 0.259 and 0.246, respectively). In a sensitivity analysis using an acquired-like burden metric that excluded OXA-51 family hits, bla _ADC family hits, predefined intrinsic or conserved chromosomal background loci, and non-antibiotic resistance classes, the median burden decreased from 17 to 9 hits per genome. Under this filter, acquired-like burden remained associated with IS/mobile genetic element burden (rho = 0.237) and showed a slightly stronger association with plasmid replicon diversity (rho = 0.285), with both relationships persisting after excluding genomes from China and the United States. Mobilome features remained markedly heterogeneous across lineages, whereas virulence-associated gene presence profiles were comparatively conserved. Conclusions: These findings support a lineage-structured view of resistance-associated genomic variation in A. baumannii. However, the observed genome-wide associations were small in magnitude and should be interpreted as patterns of co-occurrence rather than direct evidence of mechanism or causality. Sensitivity analyses suggest that plasmid-related features show a more robust relationship with acquired-like resistance burden than IS counts alone. This distinction is relevant for genomic surveillance, but it should be interpreted together with lineage imbalance, sampling bias, and the limitations of gene-presence-based inference.