Membrane-Focused Strategies Against Acinetobacter baumannii: The Therapeutic Potential of Functional Copolymers

Antimicrobial resistance is a serious global public health concern, with Acinetobacter baumannii recognized as one of the most problematic multidrug-resistant (MDR) pathogens. This Gram-negative bacterium is highly persistent in the environment, possesses a remarkably adaptable cell envelope, and forms biofilms. As the effectiveness of conventional antibiotics declines, alternative strategies are being actively explored, particularly membrane-targeting approaches based on synthetic copolymers. These compounds mimic antimicrobial peptides, offer enhanced stability and structural tunability, and have a lower propensity to develop resistance. Recent advances in polymer chemistry have led to the design of antibacterial polymers with activity against MDR A. baumannii. Some of these act synergistically with existing antibiotics, restoring bacterial susceptibility or disrupting biofilms. However, their non-degradability remains a concern due to its potential implications for body/environment accumulation and related toxicity and/or selection of resistant strains. This review examines the biology of the A. baumannii cell envelope, its resistance mechanisms, and treatment limitations, while emphasizing the promise of membrane-active copolymers. By bridging materials science and microbiology, these approaches offer promising strategies for combating World Health Organization priority pathogens.