In Silico Bioprospection of Daniellia oliveri- Based Products as Quorum Sensing Modulators of Escherichia coli SdiA

Abstract

Escherichia coli is a common pathogen responsible for various gut-related infections, and it utilizes the SdiA-mediated quorum sensing (QS) system to regulate biofilm formation, other virulence factors, and pathogenicity. With rising antibiotic resistance, there is a pressing need to discover alternative QS inhibitors (QSIs) targeting SdiA. This study evaluated 239 phytochemicals from Daniellia oliveri as potential SdiA modulators using in silico techniques. Virtual screening identified four lead compounds (cadala-1(10),3,8-triene, carotenoid K, valencene, and β-sesquiphellandrene), with carotenoid K (-53.71 kcal/mol) exhibiting a higher binding free energy compared to the standard, azithromycin (-52.19 kcal/mol), following dynamics simulation. Notably, the SdiA-carotenoid K complex demonstrated enhanced thermodynamic stability with a root mean square deviation (RMSD) of 2.64 Å. All four leads, except carotenoid K, conformed to the Lipinski rule for selection of candidates that could be administered orally. Quantum chemical feature analyses using DFT/B3LYP showed that carotenoid K had the lowest HOMO-LUMO energy gap, high ionization energy, and electrophilicity index values, indicating its superior reactivity and stability. These properties suggest enhanced interactions with the SdiA active site compared to other investigated compounds. These observations highlight carotenoid K as a promising modulator of SdiA. However, further structural modification and validation through in vitro and in vivo studies are recommended.

Keywords: Daniellia oliveri; E.coli; MD simulation; SdiA; molecular docking; quorum sensing.

Figure 1

2D docking interactions of top four D. oliveri compounds and standard. (a) Cadala-1(10),3,8-triene; (b) carotenoid K; (c) valencene; (d) β-sesquiphellandrene; (e) azithromycin.

Figure 2

Validation of the docking technique via superimposition of lead compounds and standard on the co-crystal structure of E. coli SdiA (RMSD: 0.5 Å). Cadala-1(10),3,8-triene (red); carotenoid K (pink); glycerol (native ligand, black); azithromycin (purple).

Figure 3

Comparative post-MD simulation plots of the alpha-carbon, the top four compounds, and azithromycin against the E. coli SdiA active site over a 200-ns MD simulation period. (a) Root mean squared deviation (RMSD) plots; (b) radius of gyration; (c) root mean square deviation (RMSF); (d) solvent accessible surface area (SASA).

Figure 4

Time evolution of the number of intramolecular hydrogen bonds formed following binding of the top four D. oliveri compounds and azithromycin at the E. coli SdiA active site over a 200-ns MD simulation period.

Figure 5

Frontier orbitals of the top four D. oliveri compounds. (a) Cadala-1(10),3,8-triene; (b) carotenoid K; (c) valencene; (d) β-sesquiphellandrene.

Figure 6

Electrostatic potential (ESP) mapped molecular surface of top four D. oliveri compounds. (a) Cadala-1(10),3,8-triene; (b) carotenoid K; (c) valencene; (d) β-sesquiphellandrene.