J Appl Microbiol. 2023 Dec 26:lxad316. doi: 10.1093/jambio/lxad316. Online ahead of print.
ABSTRACT
AIMS: To evaluate the antifungal and antibiofilm activity of gallic acid derivatives TPP+-C10 and TPP+-C12 and their effects on mitochondrial function on two C. albicans reference strains (ATCC 90029 and ATCC 10231).
METHODS AND RESULTS: First, we determined minimal inhibitory concentration using a microdilution assay. Both compounds exerted antifungal effects, and their minimal inhibitory concentrations (MICs) ranged from 3.9 to 13 μM, with no statistically significant differences between them (P > 0.05, t-test). These concentrations served as references for following assays. Subsequently, we measured oxygen consumption with a Clark electrode. Our observations revealed that both drugs inhibited oxygen consumption in both strains with TPP+-C12 exerting a more pronounced inhibitory effect. We then employed flow cytometry with TMRE as a probe to assess mitochondrial membrane potential. For each strain assayed, the compounds induced a decay in transmembrane potential by 75% to 90% compared to the control condition (P < 0.05, ANOVA). Then, we measured ATP levels using a commercial kit. TPP+-C12 showed a 50% decrease of ATP content (P < 0.05 ANOVA), while TPP+-C10 exhibited a less pronounced effect. Finally, we assessed the antibiofilm effect using the MTT reduction assay. Both compounds were effective, but TPP+-C12 displayed a greater potency, requiring a lower concentration to inhibit 50% of biofilms viability (P < 0.05, t-test).
CONCLUSIONS: Derivatives of gallic acid linked to a TPP+ group exert antifungal and antibiofilm activity through impairment of mitochondrial function in C. albicans.
PMID:38148145 | DOI:10.1093/jambio/lxad316
