New Insights into Acinetobacter baumannii Pathogenesis and Therapeutic Implications

Acinetobacter baumannii is a leading cause of healthcare-associated infections and is classified among the highest-priority antimicrobial-resistant pathogens. Its clinical success reflects the convergence of antimicrobial resistance (AMR) and biological traits that promote environmental persistence and transmission. Acinetobacter baumannii has undergone a remarkable transformation over the past few decades, evolving from a relatively obscure environmental bacterium into a globally recognized multidrug-resistant pathogen. Its prevalence in healthcare settings, particularly intensive care units, has made it a leading cause of ventilator-associated pneumonia, bloodstream infections, wound infections, and urinary tract infections. Beyond its antibiotic resistance, the bacterium’s ability to persist in hospital environments and adapt to host defences has amplified its clinical significance. Recent research has uncovered complex networks of virulence factors, regulatory systems, and metabolic strategies that enable A. baumannii to thrive in hostile environments and evade host immunity, providing new insights into its pathogenesis and potential therapeutic vulnerabilities. This review summarizes the main mechanisms underlying its pathogenicity, including desiccation tolerance, biofilm formation, disinfectant resistance, metal acquisition, motility, and the ability to enter viable but non-culturable states. In A. baumannii, AMR functions as a pathogenesis-adjacent trait, enhancing survival and clonal dissemination through genomic plasticity, resistance islands, efflux systems, and envelope remodeling. Key resistance pathways involve carbapenem-hydrolyzing oxacillinases, metallo-β-lactamases, permeability defects, and multidrug efflux, often coexisting within high-risk clones. From a clinical perspective, management of carbapenem-resistant strains requires accurate infection diagnosis, reliable susceptibility testing, site-specific and PK/PD-optimized therapy, and early reassessment. Overall, the success of A. baumannii reflects the integration of resistance and persistence within healthcare ecosystems, highlighting the need for coordinated strategies combining stewardship, infection control, improved diagnostics, and anti-biofilm or anti-virulence approaches.