Abstract
PURPOSE: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris. METHODS: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model. RESULTS: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC(50%) and MIC(90%) of CHGX-DME against C. auris isolates ranged from 50-200 mg/L and 100-400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection. CONCLUSION: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.