Virulence and Resistance Mechanisms in Multidrug-Resistant Acinetobacter baumannii

Acinetobacter baumannii, a Gram-negative opportunistic bacterium in the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.), has emerged as a leading cause of nosocomial infections worldwide. It is known to possess diverse virulence traits and antimicrobial resistance, making it a critical priority pathogen on the World Health Organization’s 2024 Bacterial Priority Pathogens List. Carbapenem-resistant A. baumannii (CRAB) is currently endemic across several continents, with global carbapenem resistance exceeding 70% in healthcare settings and multidrug-resistant infections being associated with alarming mortality rates. This review comprehensively discusses the molecular underpinnings of A. baumannii pathogenesis and virulence, detailing the array of factors coordinated by complex regulatory networks. The convergence of this pathogen’s virulence and antimicrobial resistance traits, resulting in multidrug resistance, leaves clinicians with only a handful of therapeutic options. The review also discusses upcoming therapeutic strategies, including phage therapy, antimicrobial peptides, monoclonal antibodies, photodynamic therapy, and vaccine candidates in the pipeline. While emerging therapeutics show promise, several challenges remain, and integrated approaches are warranted to efficiently combat A. baumannii’s virulence and resistance armamentarium.