Novel plasmid curing mediated restoration of antimicrobial sensitivity by Nigella sativa extract against multidrug resistant Staphylococcus aureus

Plasmid-mediated antimicrobial resistance is a major contributor to infections associated with high morbidity and mortality. Given the urgent demand for effective and safe elimination of plasmids from multidrug-resistant (MDR), this study is the first to examine the potential of Nigella sativa essential oil (NSO) and thymoquinone (TQ) in eliminating antimicrobial resistance plasmid from Staphylococcus aureus. Plasmid profiles of resistant variants derived from the original MDR strains following exposure to sublethal concentrations of NSO and TQ were analyzed and compared with those of the untreated parent strains using agar gel electrophoresis. Computational analyses were performed to evaluate the interactions between eleven phytoconstituents of Nigella sativa constituents and cytidylyltransferase (CTP) and glutamine amidotransferase (Gat-D) enzymes, which are involved in cell wall biosynthesis. NSO and TQ exhibited plasmid- curing and MDR reversal effects comparable to SDS. Remarkably, their combination with antimicrobials or SDS resulted in superior plasmid elimination efficiency. The eleven NSO constituents demonstrated moderate to strong binding affinities with CTP and Gat-D enzymes, thereby impairing their catalytic function by obstructing substrate interaction. The plasmid curing property offers a novel therapeutic strategy for combating antibiotic resistance by eliminating resistance genes from infectious S. aureus.