Abstract
Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of Nigella sativa essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, S. epidermidis ATCC 12228 and Candida albicans ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5–50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25–100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1–6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25–50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25–100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from Thermus thermophilus, transcriptional regulator qacR from Staphylococcus aureus, N-myristoyltransferase from Candida albicans, and NADPH-dependent D-xylose reductase from Candida tenuis. In contrast, the nitroreductase family protein from Bacillus cereus and spore coat polysaccharide biosynthesis protein from Bacillus subtilis and UDP-N-acetylglucosamine pyrophosphorylase from Aspergillus fumigatus are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ’s high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and Candida albicans.
Highlights
Hospital-acquired infections caused by multi-drug resistant (MDR) pathogens are among the leading causes of mortality in hospitalized patients [1,2,3,4,5]
Preliminary antimicrobial activity tests revealed that TQ exhibits substantial antibacterial activity against all Gram-positive bacteria tested at a concentration of 200 μg/disc
The results further show that P. vulgaris ATCC 6380 is the most susceptible bacterium, as it could not survive until the first hour of incubation, while S. aureus ATCC
Summary
Hospital-acquired infections caused by multi-drug resistant (MDR) pathogens are among the leading causes of mortality in hospitalized patients [1,2,3,4,5] These pathogens include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococci (VRE), and extended-spectrum beta-lactamase (ESBL) producing organisms, including Escherichia coli (E. coli) Pseudomonas aeruginosa (P. aerugenosa), Acinetobacter baumannii (A. baumannii), Klebsiella pneumoniae (K. pneumoniae), Klebsiella oxytoca (K. oxytoca), Proteus mirabilis (P. mirabilis), Salmonella enterica (S. enterica), Neisseria gonorrhoeae (N. gonorrhoeae), Haemophilus influenzae (H. influenzae), Kluyvera species, and Enterobacter aerogenes (E. aerogenes). The discovery of novel antimicrobial drugs and drug targets is necessary to combat potentially fatal MDR infections [1].
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