Pioneering study of Egyptian Neem and Jojoba extracts with molecular docking combat hospital multidrug resistant bacteria.

Abstract

Hospital surfaces are often contaminated with multidrug-resistant pathogenic bacteria that cause healthcare-associated infections and lead to increased mortality and morbidity. There is a need for new alternative antibacterial agents to overcome antibiotic resistance. Azadirachta indica and Simmondsia chinensis have been found to possess antibacterial activity and medicinal value. The antibacterial activity of these plant extracts against clinical isolates was investigated using the agar disc diffusion method. These clinical isolates included E. coli, Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella pneumoniae, Stenotrophomonas maltophilia, and methicillin-resistant Staphylococcus aureus (MRSA), which were identified by the vitek-2 system, and resistance genes of selected bacterial strains were identified by using the bioFire FilmArray test. The most potent extract of these plants was the ethanolic extract, where the inhibition percentage of ethanolic Jojoba and Neem extracts was 90.9% and 74.5%, respectively against all the tested pathogens. On the other hand, the methanolic extracts of Neem and Jojoba have different degrees of antibacterial activity against the tested pathogens. The phytochemical components of the most potent extracts (ethanolic extracts) were investigated by gas chromatography‒mass spectrometry (GC\MS), which revealed that the ethanolic extracts were enriched in phenolics, flavonoids, and sugars. FTIR analyses of the plant extracts confirmed the presence of alcoholic, carboxylic, and aldehydic moieties. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity of the ethanolic extracts of Neem and Jojoba increased in a dose-dependent manner, with average IC50 values of 98.17 ± 0.85, 4.95 ± 0.06, and 4.17 ± 0.04 mg/mL, respectively, for the ethanolic Neem extract, the ethanolic Jojoba extract, and ascorbic acid (standard). Furthermore, increased cytotoxicity was demonstrated in the HFB4 cell line in a dose-dependent manner. The average IC50s of the ethanolic Neem extract and the ethanolic Jojoba extract were 18.18 ± 0.15 and 76.16 ± 1.49 mg/mL, respectively. Moreover, the results for the antibiofilm activity of the ethanolic Neem extract showed that 99.5% of the biofilms formed at 25 mg/ml. In addition, 50 mg/ml of the ethanolic extract of Jojoba had a suppressive effect of 98.2%. The significant components Nonanoic acid (21.9405%) and Palmitic Acid (16.0869%) from Neem and pinitol from Jojoba (82.85%) were selected throughout the molecular docking investigation, by which the chosen constituents inhibited the crystal structure of penicillin-binding protein 4 (PBP4) from Staphylococcus aureus (PDB ID: 1TVF) and the crystal structure of the OXA-48 beta-lactamase (PDB ID: 7AUX) from K. pneumoniae. Overall, our study reveals the effectiveness of antimicrobial plant extracts as therapeutic solutions for antibiotic resistance in Egypt and worldwide with some modifications to decrease their cytotoxicity.