Natural compounds targeting multidrug-resistant Acinetobacter baumannii: Anti-Biofilm, anti-resistance, and synergistic strategies.

Acinetobacter baumannii has emerged as a major cause of nosocomial infections. The emergence of drug-resistant strains has made most current antibiotics ineffective. The limited number of antibiotics currently in development has prompted the development of innovative strategies. One of these strategies is the use of natural compounds with potent antibacterial activity. Among them, carvacrol, thymol, cinnamaldehyde, curcumin, quercetin, eucalyptol, linalool, catechin, limonene, geraniol, coumarin, and eugenol have demonstrated considerable activity against A. baumannii. Natural compounds primarily act by compromising the integrity of the cell membrane, leading to leakage of intracellular contents and cell lysis and death. These compounds also inhibit ATP synthesis, induce oxidative stress, and interact with OmpA. Inhibition of efflux pumps, interaction with enzymes such as PBP, OXA, IMP, VIM, and NDM, disruption of secretion systems, and induction of DNA damage are among the mechanisms by which these compounds act against antibiotic resistance and may help limit the emergence of further resistance. Natural compounds also showed synergistic effects with conventional antibiotics, including imipenem, ciprofloxacin, gentamicin, and colistin, and could re-sensitize bacteria to these agents. To enhance the antibacterial and antibiofilm activity of natural compounds, nanoformulations have been used as effective vehicles, improving their bioavailability and therapeutic effectiveness. These findings provide valuable insights into the potential of natural compounds as effective agents against A. baumannii and its biofilm, offering promising avenues for developing novel strategies to prevent and manage drug-resistant A. baumannii infections, overcome antibiotic resistance, and provide a foundation for future therapeutic innovations.