AUTHOR=Guo Tingting , Li Mengying , Sun Xiaoli , Wang Yuhang , Yang Liying , Jiao Hongmei , Li Guocai 

TITLE=Synergistic Activity of Capsaicin and Colistin Against Colistin-Resistant Acinetobacter baumannii: In Vitro/Vivo Efficacy and Mode of Action

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.744494

DOI=10.3389/fphar.2021.744494

ISSN=1663-9812

ABSTRACT=<p><italic>Acinetobacter baumannii</italic> 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 <italic>Acinetobacter baumannii</italic> strains <italic>in vitro</italic> and <italic>in vivo</italic>, 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 <italic>A. baumannii</italic>. A mouse bacteremia model confirmed the <italic>in vivo</italic> effects of capsaicin and colistin. Mechanistic studies shown that capsaicin can inhibit the biofilm formation of both colistin-resistant and non-resistant <italic>A. baumannii.</italic> In addition, capsaicin decreased the production of intracellular ATP and disrupted the outer membrane of <italic>A. baumannii.</italic> In summary, the synergy between these drugs may enable a lower concentration of colistin to be used to treat <italic>A. baumannii</italic> infection, thereby reducing the dose-dependent side effects. Hence, capsaicin–colistin combination therapy may offer a new treatment option for the control of <italic>A. baumannii</italic> infection.</p>