Schisandrins as novel efflux pumps inhibitors and non-antibiotic compounds against multi- and extensively-drug resistant clinical strains of Salmonella typhi: An in-vitro study.

PURPOSE: Typhoid is a significant global health challenge due to its high pathogenicity and antimicrobial resistance. Salmonella typhi (S.typhi) can switch its lifestyles between biofilm and planktonic phase which allows it to evade host defenses and develop resistance to antibiotics. Salmonella sp. harbors multiple genes encoding efflux-pumps systems whose up-regulation contributes to multi-drug resistance (MDR) and extensive drug-resistance (XDR). To overcome the battle against resistant S. typhi strains, novel non-antibiotics inhibitors are required for inhibitory application. This study assesses the inhibitory effect of lignans against drug resistance of S. typhi.

METHODS

Clinical resistant and sensitive strains of S. typhi were obtained and characterized. The inhibitory effect of lignans, specifically Schisandrin A and B, purified from the plant Schisandra chinensis, are found to be effective non-antibiotic inhibitors were evaluated through standard microbiological techniques like growth curve and time-kill assays. Impact on bacterial morphology was analyzed using scanning electron microscopy (SEM). Our study explores two approaches, such as efflux pumps (EPs) inhibition and antibiofilm assays.

RESULTS

Using colony-forming unit (CFU) assays, growth curve analysis, and SEM imaging, we observed significant bacteriostatic effects, with Schisandrin B causing notable membrane disruption. Schisandrin B also showed remarkable biofilm inhibition (90.33%) and strong efflux pumps inhibition.

CONCLUSION

This study offers a strong basis for future research on addressing antibiotic resistance in clinically relevant pathogens.