Integrated genomic and structural analysis of Acinetobacter baumannii biofilm and anti-biofilm studies with flavone

Acinetobacter baumannii is a clinically significant pathogen due to its rapid acquisition of multidrug resistance (MDR) and its robust biofilm-forming ability, which contributes to treatment failure. Hence, the current study was designed to examine the structural, biochemical, and genomic characteristics, as well as the antibiofilm potential, of the phytochemical flavone in mature biofilms. Structural and biochemical analysis revealed that the tested clinical isolate produced a thick extracellular polymeric substance (EPS) matrix enriched in polysaccharides and proteins. Whole-genome sequencing (WGS) identified virulence factors such as AdeFGH efflux pumps, PNAG biosynthesis systems, which are crucial in biofilm formation, and resistance determinants, including β-lactamases (ADC-76, OXA-68), fluoroquinolone resistance mutations in parC that contribute to its antimicrobial resistance. Further, the antimicrobial assays demonstrated that flavone inhibited planktonic growth, and biofilm inhibition studies revealed concentration-dependent disruption of mature biofilms, with bactericidal and antibiofilm effects observed at 2xMIC levels. Drug-likeness and pharmacokinetic evaluation using SwissADME indicated that flavone meets the major criteria for oral drug-likeness. Overall, these findings provide integrated insights into A. baumannii biofilm biology and support flavone as a promising natural candidate for combating biofilm-mediated survival in drug-resistant A. baumannii.