Synergistic Activity of Capsaicin and Colistin Against Colistin-Resistant : In Vitro/Vivo Efficacy and Mode of Action.

is an opportunistic pathogen predominantly associated with nosocomial infections. With emerging resistance against polymyxins, synergistic combinations of drugs are being investigated as a new therapeutic approach. Capsaicin is a common constituent of the human diet and is widely used in traditional alternative medicines. The present study evaluated the antibacterial activities of capsaicin in combination with colistin against three unrelated colistin-resistant strains and , and then further studied their synergistic mechanisms. Using the checkerboard technique and time-kill assays, capsaicin and colistin showed a synergistic effect on colistin-resistant . A mouse bacteremia model confirmed the effects of capsaicin and colistin. Mechanistic studies shown that capsaicin can inhibit the biofilm formation of both colistin-resistant and non-resistant In addition, capsaicin decreased the production of intracellular ATP and disrupted the outer membrane of In summary, the synergy between these drugs may enable a lower concentration of colistin to be used to treat infection, thereby reducing the dose-dependent side effects. Hence, capsaicin-colistin combination therapy may offer a new treatment option for the control of infection.