Structure-based drug discovery targeting fmhA in Staphylococcus warneri using extracts of Calliandra harrisii : an integrated ethnobotanical and in silico approach

Abstract Staphylococcus warneri is a Gram-positive bacterium increasingly associated with urinary tract and skin infections and shows emerging multidrug resistance. In this study, S. warneri was cultured, and the virulence-associated fmhA gene was amplified, sequenced, and submitted to GenBank, representing the first reported molecular characterization of fmhA in this species. An ethnobotanical approach guided the selection of Calliandra harrisii for antimicrobial evaluation. Methanolic Soxhlet extraction followed by GC-MS analysis identified multiple bioactive phytochemicals. The three-dimensional structure of the Aminoacyl-transferase FemA ( fmhA ) protein was modeled and validated, showing acceptable structural quality. Selected phytochemicals were screened using ADME criteria, molecular docking, and molecular dynamics simulations. Among them, spiro[1,3-dioxolane-2,2′-[6,7] diazabicyclo[3.2.2] non-6-ene] demonstrated favorable binding affinity, structural stability during 100 ns simulations, and energetically favorable MM/GBSA and MM/PBSA profiles. Density functional theory analysis revealed a moderate HOMO–LUMO gap, supporting balanced chemical reactivity and stability. Pharmacophore modeling and in silico toxicity prediction further suggested acceptable drug-likeness and low oral toxicity. Collectively, this integrated ethnobotanical and in silico framework identifies C. harrisii as a promising source of antibacterial agents and highlights spiro[1,3-dioxolane-2,2′-[6,7]diazabicyclo[3.2.2] non-6-ene] as a potential lead compound targeting fmhA in S. warneri . Experimental validation is warranted to confirm its therapeutic potential.