Comparative genomics of carbapenem resistant and susceptible clinical Acinetobacter baumannii reveals lineage-associated mobilization of acquired carbapenemase determinants: an integrative in silico genomics approach

Abstract

Background Carbapenem resistant Acinetobacter baumannii (CRAB) is recognized as one of the most critical priority pathogens by the World Health Organization due to its persistence in nosocomial settings, extensive antimicrobial resistance, and increasing dissemination at the global level. Despite the escalating availability of genomic data, genotype–phenotype integrated studies exploring the genetic determinants associated with carbapenem resistance remain limited. Methods In this study, a comprehensive comparative genomics was performed using publicly available 395 clinical A. baumannii genomes, comprising of 267 CRAB and 128 carbapenem susceptible A. baumannii (CSAB). Comparative genomic analyses included sequence types (STs), virulence factors (VFs), antimicrobial resistance genes (ARGs), and mobile genetic elements (MGEs) characterization. Pangenome-wide association study (PanGWAS) was performed to test the associations between genotypes and carbapenem resistance phenotype. Results CRAB genome subset demonstrated higher abundance of ARGs (acquired carbapenemases in particular), plasmids, carbapenem resistance-associated insertion sequences, and integrons than CSAB genomes. PanGWAS identified six positively associated genes (relE, umuC, hphA, hsmA, hphR, and fecI) significantly enriched in CRAB population. Core SNP phylogeny integrated with STs and acquired carbapenemase genes exhibited heterogeneous distribution of resistance genes across lineages, indicating potential role of both clonal dissemination and horizontal gene transfer. Conclusion This study provides an overall genomic architecture of CRAB integrating comparative genomics, PanGWAS, and phylogenomics approaches. The findings underscore the complex interplay between ARGs, VFs, and MGEs in the genomic evolution of CRAB, expanding current understanding of CRAB adaptation and may contribute toward enhanced surveillance, antimicrobial stewardship, and exploration of alternative therapeutic targets.