Convergent evolution of ST2 and ST164 mediates dissemination of the blaNDM-1/blaOXA-23 profile in Acinetobacter baumannii
摘要
The convergence of the potent carbapenemase genes blaNDM-1 and blaOXA-23 in carbapenem-resistant Acinetobacter baumannii (CRAB) poses a critical threat. However, the dissemination patterns and evolutionary drivers of this dual-carbapenemase profile remain unclear.
MethodsWe performed a comprehensive genomic analysis of a global collection of 1820 high-quality public WGS-derived CRAB isolates (2001–2024) harbouring acquired non-OXA carbapenemase genes. Topological congruence between blaNDM-1- and blaOXA-23-positive phylogenies was assessed via normalized Robinson-Foulds (nRF) distance. Ecological diversity metrics (e.g., Shannon entropy) combined with Bayesian and hypergeometric models quantified host-lineage restriction. The evolutionary dynamics of a colistin-resistant ST2 sublineage (PmrB T232I) were inferred using Skygrowth coalescent analysis. Geographic divergence was assessed via PERMANOVA and genome-wide association study (GWAS).
ResultsCo-occurring acquired carbapenemase genes dominated the cohort, with the combination of blaNDM-type and blaOXA-23-like genes accounting for 64.7% (1178/1820) of isolates. This prevalence was primarily driven by the specific blaNDM-1/blaOXA-23 profile (n = 1080), overwhelmingly restricted to two clones: the internationally disseminated ST2 (n = 644) and the regionally prevalent ST164 (n = 209). An integrated triad of evidence—topological congruence (nRF = 0.346, p < 0.001), a mathematically stark collapse in lineage diversity upon dual-gene acquisition, and extreme statistical enrichment (Bayes factors 7.8 × 1019–1.5 × 1022)—demonstrates that this dual-resistance phenotype does not diffuse randomly via horizontal transfer. Instead, it is profoundly constrained within these specific accommodating clonal frameworks. Within the dominant ST2 clone, a colistin-resistant high-risk sublineage exhibited a ‘gene load–selection continuum’, where a subgroup with an expanded resistome paradoxically maintained a higher effective population size, highlighting the role of genomic plasticity. Geographic origin explained 46.5% of accessory genome variance (PERMANOVA p < 0.001), highlighting strong geographic stratification of accessory genomes.
ConclusionsThe widespread dissemination of the blaNDM-1/blaOXA-23 profile is mediated by the convergent expansion of ST2 and ST164, acting as dominant clonal drivers. This study provides a framework for clone-specific epidemiological hitchhiking and highlights the need to refine surveillance to prioritize the genomic tracking of these key lineages. The retrospective nature of public data may influence prevalence estimates, but the core clonal dissemination pattern remains robust.