In silico and In vitro combinatorial study in the fight against the multi-drug resistant uropathogen, Pseudomonas aeruginosa | ||||
| Microbes and Infectious Diseases | ||||
| Article 20, Volume 5, Issue 4, November 2024, Page 1438-1449 PDF (981.18 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/mid.2023.217574.1542 | ||||
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| Authors | ||||
Samuel Oluwatoyin Titiladunayo   ; Muftau Kolawole Oladunmoye
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| Department of Microbiology, School of Life Science, Federal University of Technology, Akure, Ondo state, Nigeria | ||||
| Abstract | ||||
| Background: The emergence of drug-resistant pathogens has been found to increase mortality and the therapeutic cost of infections around the world. Pseudomonas aeruginosa (P. aeruginosa), one of the multi-drug resistant pathogens, causes nosocomial and urinary tract infections. The increasing concerns about its morbid effects and resultant mortality have provoked intensive studies on alternative therapeutic solutions to the challenge posed by multidrug-resistant pathogens. Therefore, this study combines in vitro and in silico models to investigate the antimicrobial potential of Azadirachta indica (A. Juss) and Phyllanthus amarus (P. amarus) (Schum and Thonn) leaves of ethanolic extract on multidrug-resistant pathogenic P. aeruginosa. Methods: Standard procedures were used for the preparation of extracts, phytochemical screening, minimum inhibitory concentration, minimum bactericidal concentration, fractional inhibitory concentration, mechanism of action and gas chromatography-mass spectrophotometer (GCMS). In silico study was carried out by molecular docking of the extracts with MexB-resistant protein encoding the 6IIA-resistant gene of P. aeruginosa. Results: Many of the ligands had high docking scores which indicate a strong potential for use as drugs to counter the resistant genes. Ligands like Oleanolic acid (-9.8kcal/mol), of P. amarus and Azadirachtol (-10.2kcal/mol) of A. indica, had the best docking scores. The sensitivity assay done using P. aeruginosa as a target revealed that both A. indica and P. amarus were able to effectively inhibit the uropathogen at 350mg/ml concentration and with the same zone of inhibition of 20.50±0.33. The minimum inhibitory concentration result revealed that A. indica (300mg/ml) is less effective when compared to P. amarus (200mg/ml). The minimum bactericidal result revealed in a similar fashion that P. amarus (300mg/ml) was more effective than A. indica (350mg/ml) because of the lesser concentration required. Fractional inhibitory concentration shows that the combination of A. indica and P. amarus gives an additive effect (0.83). Mechanism of action result showed that the release of Sodium content was more in P. amarus (17.3Mol/L) than A. indica (12.3Mol/L) and it was released the least in protein (1.0Mol/L- A. indica; 3.6Mol/L- P. amarus). Conclusion: The in-silico studies revealed that A. indica had the ligand with the best docking score and greatest potential, while the in-vitro investigation revealed that P. amarus had a higher antibacterial potency against the multidrug resistant uropathogen P. aeruginosa than A. indica. | ||||
| Keywords | ||||
| Uropathogenic; multidrug-resistant; Azadirachta indica; Phyllanthus amarus; In silico-study | ||||
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