Revealing anti-fungal potential of plant-derived bioactive therapeutics in targeting secreted aspartyl proteinase (SAP) of Candida albicans: a molecular dynamics approach.

Candida species have established themselves as a major source of nosocomial infections. Increased expression of secreted aspartyl proteinases (SAP5) plays a crucial role in the pathogenesis of Candida species. Phytotherapeutics continue to serve as a viable resource for discovering novel antifungal agents. Hence the main aim of the present investigation is to explore the possible inhibitory role of the selected bioactive molecules against the SAP5 enzyme of C. albicans using in silico approach. Molecular docking and dynamic simulations were utilized to predict the binding affinity of the lead molecules using the AutoDock and Gromacs in-silico screening tools. Results of preliminary docking simulations show that the compounds hesperidin, vitexin, berberine, adhatodine, piperine, and chlorogenic acid exhibit significant interactions with the core catalytic residues of the target protein. The best binding ligands (hesperidin, vitexin, fluconazole) were subjected to molecular dynamics (MD) and essential dynamics of the trajectories. Results of the MD simulation confirm that the ligand-protein complexes became more stable from 20 ns until 100 ns. The calculated residue-level contributions to the interaction energy along a steady simulation trajectory of all three hits (hesperidin (-132.720 kJ/mol), vitexin (-83.963 kJ/mol) and fluconazole (-98.864 kJ/mol)) ensure greater stability of the leads near the catalytic region. Essential dynamics of PCA and DCCM analysis signifies that the binding of hesperidin and vitexin created a more structurally stable environment in the protein target. The overall outcomes of this study clearly emphasize that the bioactive therapeutics found in medicinal herbs may have remarkable scope in managing Candida infection.

Enhancement of antimicrobial activity by liposomal oleic acid-loaded antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa.

In this study, we examined the efficacy of liposomal oleic acid-based antibiotic formulations on 32 strains of multidrug-resistant Pseudomonas aeruginosa (MDRPa). The average size of liposomes were 93.12 ± 2.3 nm holding a negative zeta potential at -57.3 ± 0.89. Liposomal antibiotic formulations were tested against 32 MDRPa strains isolated from burn wounds and urine samples, which exhibited an MIC of ≤8 µg/mL, whereas MIC of free antibiotics ranged from 32 to >1024 µg/mL. The results clearly indicate that the liposomes composed of naturally occurring oleic acid, could be used therapeutically either alone or in combination with antibiotics to effectively treat P. aeruginosa infections.