Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Abstract

Isobavachalcone (IBC) is a natural flavonoid with multiple pharmacological properties. This study aimed to evaluate the efficacy of IBC against planktonic growth and biofilms of Candida albicans (C. albicans) and the mechanisms underlying its antifungal action. The cell membrane integrity, cell metabolic viability, and cell morphology of C. albicans treated with IBC were evaluated using CLSM and FESEM analyses. Crystal violet staining, CLSM, and FESEM were used to assess the inhibition of biofilm formation, as well as dispersal and killing effects of IBC on mature biofilms. RNA-seq combined with apoptosis and autophagy assays was used to examine the mechanisms underlying the antifungal action of IBC. IBC exhibited excellent antifungal activity with 8 μg/mL of MIC for C. albicans. IBC disrupted the cell membrane integrity, and inhibited biofilm formation. IBC dispersed mature biofilms and damaged biofilm cells of C. albicans at 32 μg/mL. Moreover, IBC induced apoptosis and autophagy-associated cell death of C. albicans. The RNA-seq analysis revealed upregulation or downregulation of key genes involved in cell wall synthesis (Wsc1 and Fks1), ergosterol biosynthesis (Erg3, and Erg11), apoptisis (Hsp90 and Aif1), as well as autophagy pathways (Atg8, Atg13, and Atg17), and so forth, in response to IBC, as evidenced by the experiment-based phenotypic analysis. These results suggest that IBC inhibits C. albicans growth by disrupting the cell wall/membrane, caused by the altered expression of genes associated with β-1,3-glucan and ergosterol biosynthesis. IBC induces apoptosis and autophagy-associated cell death by upregulating the expression of Hsp90, and altering autophagy-related genes involved in the formation of the Atg1 complex and the pre-autophagosomal structure. Together, our findings provide important insights into the potential multifunctional mechanism of action of IBC.

Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans

“…19 A recent study has demonstrated the antifungal properties of IBC against C. albicans. 23 However, the specific target proteins responsible for this activity remain unidentified. In the current investigation, we utilized DARTS and chemical genomics techniques to identify Eno1 as the target protein of IBC against C. albicans.…”

“…A recent study has demonstrated the antifungal properties of IBC against C. albicans . However, the specific target proteins responsible for this activity remain unidentified.…”

“…22 A recent study highlighted the antifungal and antibiofilm capabilities of IBC against C. albicans, attributing these effects to the disruption of cell wall and membrane integrity, as well as the induction of apoptosis and autophagy. 23 Despite these findings, specific antifungal mechanisms of IBC against C. albicans remain largely unexplored. In this investigation, it was determined that IBC exhibits significant antifungal properties against FLC-resistant pathogenic fungi both in vitro and in vivo.…”

“…A recent study highlighted the antifungal and antibiofilm capabilities of IBC against C. albicans, attributing these effects to the disruption of cell wall and membrane integrity, as well as the induction of apoptosis and autophagy . Despite these findings, specific antifungal mechanisms of IBC against C.…”

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species

“…Approximately 30 worms in M9 buffer with or without NBP at concentrations of 2, 10, 20, 50, 100, 200, and 400 µg/ml were placed in 96-well plates and incubated for 10 days at 25°C without agitation. The percentage of live worms was determined by the responses of the worms to LED light exposure for 20–30 s using an iRiS Digital Cell Imaging System after incubation ( Qian et al., 2024 ).…”