Virulence arsenal of Acinetobacter baumannii: mechanisms driving persistence and resistance

Acinetobacter baumannii is a Gram-negative opportunistic pathogen and a major cause of healthcare-associated infections, including ventilator-associated pneumonia, bacteraemia, meningitis, and urinary tract infections. Its persistence in hospital environments is due to its ability to survive desiccation, resist disinfectants, and colonize both biotic and abiotic surfaces. Virulence in A. baumannii is largely associated with structures such as Csu pili, biofilm-associated protein (Bap), and outer membrane protein A (OmpA), which enable surface attachment, biofilm formation, and host cell damage. The production of extracellular polysaccharides and quorum sensing further enhance biofilm development. Iron uptake systems support bacterial growth even under iron-limited conditions within the host. Resistance to polymyxins often results from lipid A modifications regulated by the PmrCAB operon and LpxL-related genes, which also reduce immune recognition via the TLR4 pathway. Phase variation allows phenotypic changes that aid immune evasion. The highly adaptable genome of A. baumannii enables rapid acquisition of multiple resistance determinants, including OXA-type carbapenemases, efflux pumps, and aminoglycoside-modifying enzymes. Due to its extensive multidrug resistance, the World Health Organization lists A. baumannii as a critical-priority pathogen. This review aims to comprehensively examine the molecular mechanisms driving its virulence and resistance, highlighting potential therapeutic targets and strategies to combat this formidable pathogen.