Frontiers in microbiology · 2026
In vitro synergistic activity of betulinic acid combined with azoles against pathogenic fungi.
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Zhang Heng, Ge Lu, Peng Mengqi, Tang Menghua, Zeng Yixin, Sun Chunmiao, Sun Yi
Аннотация
BACKGROUND: Invasive fungal infections and emerging antifungal resistance threaten global public health, demanding effective combination therapies.
OBJECTIVE: To evaluate in vitro synergistic antifungal activity of betulinic acid (BA) combined with four azoles (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], fluconazole [FLC]) against Aspergillus spp., Candida spp., Exophiala dermatitidis, and Cryptococcus neoformans.
METHODS: Per CLSI M27-A3/M38-A2, broth microdilution checkerboard assay determined BA's minimum inhibitory concentration (MIC) and synergy with azoles (n = 110); flow cytometry measured intracellular reactive oxygen species (ROS) in fungi co-cultured with BA.
RESULTS: BA alone had no antifungal activity, but showed synergy with specific azoles: BA/POS had 82.7% (43/52) synergy against Aspergillus spp., 95.2% (20/21) against E. dermatitidis, and 70% (7/10) against Candida auris (of 28 Candida spp., 28.6% synergy). BA/FLC had 55.6% (5/9) synergy against C. neoformans. Among the 110 strains, the synergy rates of BA with POS, ITR and VOR were 66.4, 10.9 and 2.7%, respectively; the BA-FLC synergy rate was 18.5% in 27 strains. BA/POS co-culture increased fungal ROS.
CONCLUSION: BA-POS reduces POS's MIC and exerts potent synergy against Aspergillus spp. and E. dermatitidis. BA has potential as an adjuvant for treating Aspergillus and E. dermatitidis infections.
OBJECTIVE: To evaluate in vitro synergistic antifungal activity of betulinic acid (BA) combined with four azoles (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], fluconazole [FLC]) against Aspergillus spp., Candida spp., Exophiala dermatitidis, and Cryptococcus neoformans.
METHODS: Per CLSI M27-A3/M38-A2, broth microdilution checkerboard assay determined BA's minimum inhibitory concentration (MIC) and synergy with azoles (n = 110); flow cytometry measured intracellular reactive oxygen species (ROS) in fungi co-cultured with BA.
RESULTS: BA alone had no antifungal activity, but showed synergy with specific azoles: BA/POS had 82.7% (43/52) synergy against Aspergillus spp., 95.2% (20/21) against E. dermatitidis, and 70% (7/10) against Candida auris (of 28 Candida spp., 28.6% synergy). BA/FLC had 55.6% (5/9) synergy against C. neoformans. Among the 110 strains, the synergy rates of BA with POS, ITR and VOR were 66.4, 10.9 and 2.7%, respectively; the BA-FLC synergy rate was 18.5% in 27 strains. BA/POS co-culture increased fungal ROS.
CONCLUSION: BA-POS reduces POS's MIC and exerts potent synergy against Aspergillus spp. and E. dermatitidis. BA has potential as an adjuvant for treating Aspergillus and E. dermatitidis infections.