Synergy of R-(–)carvone and cyclohexenone-based carbasugar precursors with antibiotics to enhance antibiotic potency and inhibit biofilm formation

Abstract

The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial. Glycomimetics, for example carbasugars, offer high potential as adjuvants, as they can inhibit metabolic pathways or biofilm formation due to their similarity to natural substrates. Here, we demonstrate the synthesis of carbasugar precursors (CSPs) and their application as biofilm inhibitors for E. coli and MRSA, as well as their synergistic effect in combination with antibiotics to circumvent biofilm-induced antibiotic resistances. This results in a biofilm reduction of up to 70% for the CSP rac-7 and a reduction in bacterial viability of MRSA by approximately 45% when combined with the otherwise ineffective antibiotic mixture of penicillin and streptomycin.