The modular chromosomal genomic plasticity mediating high level antibiotic resistance in eight clinical carbapenem-resistant Acinetobacter baumannii strains

Objective Acinetobacter baumannii, a prevalent multidrug resistant (MDR) pathogen, poses a significant threat to critically ill patients. This work aims to analyze the genomes of eight clinical carbapenem-resistant A. baumannii (CRAB) strains, and to study the mechanisms and genomic context of antimicrobial resistance for this critical pathogen. Methods Nanopore whole-genomic sequencing was performed and compared with carbapenem-susceptible A. baumannii strain to identify genomic context patterns of antibiotic resistance. Results Although some of these strains contain transferable plasmids, 121 of 122 antibiotic resistance genes (ARGs) identified are located on their chromosomes. Moreover, chromosomal ARGs clustered within recombinase-rich regions forming clear modules that are different from known resistance genomic islands. These modules are tandemly linked forming different combinations, and integrated at specific hot-spots via diverse mechanisms (direct repeats, fragment replacement, inverted repeats), suggesting that modular chromosomal plasticity leads to multidrug resistance in A. baumannii. Plasmid presence of these modules in other bacterial strains suggests they could have originated from plasmids. Conclusions We find that modular chromosomal plasticity is the primary driver of carbapenem-resistance in our collection of CRAB isolates, which is a unique evolutionary strategy different from other ESKAPE pathogens. This study provides critical insights into CRAB genomic adaptability, and informs future strategies to combat their spread.