Outperforming the β-Lactams: Integrated Docking and Antibacterial Assessment of Blighia sapida Phytochemicals Against Acinetobacter baumannii PBP1a

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii is a critical healthcare pathogen due to its resistance to multiple antibiotic classes, capacity for biofilm formation, and persistence in hospital environments. This study evaluated the antibacterial potential of Blighia sapida leaf extract against MDR A. baumannii and compared the molecular interactions of its phytochemicals with β-lactam antibiotics targeting penicillin-binding protein PBP1a. Crude extract was prepared by maceration, antibacterial activity was assessed using agar well diffusion and broth dilution methods, and phytochemicals were profiled by high-performance liquid chromatography (HPLC). Identified compounds, together with reference β-lactam antibiotics, were docked against A. baumannii PBP1a using Glide XP in Maestro (Schrödinger v2021) with MM/GBSA rescoring. The extract exhibited concentration-dependent antibacterial activity, producing inhibition zones of 14.33 ± 0.33 mm at 100 mg·mL⁻¹ and 12.67 ± 0.67 mm at 50 mg·mL⁻¹. HPLC revealed seventeen compounds, including flavonoids (quercetin, naringin, catechin, rutin hydrate, baicalin), phenolic acids (p-coumaric, caffeic, ferulic, gallic), and xanthones (mangiferin). Docking results showed that rutin hydrate (−8.176 kcal·mol⁻¹), naringin (−8.042 kcal·mol⁻¹), and baicalin (−7.578 kcal·mol⁻¹) demonstrated stronger binding affinities to PBP1a than all the standard drugs tested, surpassing even imipenem (−5.469 kcal·mol⁻¹), the best-scoring antibiotic control, through multiple hydrogen bonds with conserved residues including GLU446, GLY547, and ASP510. ADMET profiling indicated that while glycosylated flavonoids exhibited low oral bioavailability, smaller flavonoids and phenolic acids complied with druglikeness rules and displayed superior pharmacokinetic properties compared to standard antibiotics. Collectively, these findings provide mechanistic evidence that B. sapida phytochemicals may serve as promising inhibitors of A. baumannii PBP1a, offering potential leads for novel anti-resistance therapeutics.