Antifungal activity and mechanism of berberine against Cryptococcus neoformans

Abstract:

[Objective] To investigate the antifungal activity and mechanism of berberine against Cryptococcus neoformans. [Methods] The minimum inhibitory concentration (MIC) of berberine against the standard strain and clinical isolates of C. neoformans was determined by micro-broth dilution method. The synergistic effect of berberine with the marketed antifungal drugs (fluconazole and amphotericin B) was determined by checkerboard method. Further, we determined the effects of berberine on the expression of key virulence factors of Cryptococcus and on the macrophage-Cryptococcus interaction. The in vivo fungicidal activity of berberine was examined with the Galleria mellonella model of Cryptococcus infection. [Results] Berberine was a fungicidal compound with a MIC range of 8−16 µg/mL against the tested strains. Berberine at the sublethal concentration inhibited capsule size, melanin-producing ability, and sexual reproduction and enhanced the fungicidal ability of macrophages. The zinc-finger transcription factor Nrg1 mediated these important processes. The experiment with the G. mellonella model of cryptococcal infection showed that berberine prolonged the survival time of infected G. mellonella. [Conclusion] Berberine exhibits excellent anti-cryptococcal activity in vitro and in vivo and is expected to be a promising starting compound for the development of anti-cryptococcal agents.