In-silico insights into targeting OmpA: an approach to combat multidrug resistance in .

Abstract: The rise of multidrug-resistant poses significant challenges in hospital settings. This study evaluates the antimicrobial potential of the aqueous extract of (AETC) against strain AB0014, isolated from a preterm neonate presenting sepsis. The minimum inhibitory concentration (MIC) was determined using the microdilution method. Outer Membrane Protein A (OmpA) was targeted due to its role in bacterial structural integrity and pathogenicity. A protein-protein interaction (PPI) network was constructed using literature data and validated via the STRING database. Molecular docking results from AutoDock Vina and AutoDock 4.0 were further analysed, and the ligands were ranked using statistical tools such as ANOVA. AETC exhibited potent antimicrobial activity, with a 56 mm zone of inhibition and an MIC of 0.059 µg/mL. LC-MS analysis identified twelve major phytocompounds. Network analysis confirmed OmpA as a key regulatory hub in antibiotic resistance, interacting with β-lactamase genes (BlaR1, AmpC), efflux pumps (AdeB, MexR), and pathways associated with multidrug resistance. Further analysis revealed OmpA's dominance (degree = 7, betweenness = 0.85), with a low clustering coefficient (0.059), indicating network vulnerability upon inhibition. PCR confirmed the presence of in AB0014. Lipinski's Rule of Five analysis indicated that 83.33% of the phytocompounds present in the AETC met drug-likeness criteria, suggesting high bioavailability. Molecular docking identified Terminalin as the most promising inhibitors, with strong binding affinities. Further, molecular dynamics simulations demonstrated the ability to interact effectively with OmpA while maintaining or enhancing its structural dynamics. This study highlights the antimicrobial potential of AETC and its ability to target OmpA-mediated resistance in , offering a promising therapeutic strategy.