A minimalist opportunist: the emergence of Acinetobacter baumannii

ABSTRACT Acinetobacter baumannii has evolved from a relatively overlooked nosocomial pathogen into one of the most concerning multidrug-resistant threats worldwide. Its global dissemination, accelerated by healthcare-associated transmission and the emergence of carbapenem-resistant strains, has established A. baumannii as a critical priority pathogen. While initially studied primarily through the lens of antimicrobial resistance, growing evidence indicates that the remarkable success of A. baumannii cannot be attributed to resistance alone. Unlike many classical bacterial pathogens, A. baumannii lacks an extensive arsenal of virulence factors and major secretion systems. Instead, its success relies on a highly effective “persist and resist” strategy, combining intrinsic tolerance, extensive genomic plasticity, metabolic adaptability, and multilayered regulatory networks that enable survival under severe environmental and host-imposed stresses. This apparent simplicity, coupled with exceptional resilience, makes A. baumannii a particularly informative system for understanding how limited pathogenic determinants can generate profound clinical success. In this review, we highlight the key biological features that have established A. baumannii as a model system. We discuss milestone discoveries that have reshaped our understanding of its pathogenesis, emphasizing how this pathogen leverages adaptability rather than an extensive virulence arsenal to succeed as an opportunistic pathogen, expanding the field beyond antibiotic resistance toward broader questions of host-pathogen interaction and environmental adaptation. Finally, we outline major open questions in the field, including the contribution of intracellular reservoirs to chronic infection and treatment failure. Together, these perspectives position A. baumannii as a unique system for investigating how a seemingly minimalist pathogen achieves extraordinary adaptability and clinical success.