Gallic acid triphenylphosphonium derivatives TPP+-C10 and TPP+-C12 inhibit mitochondrial function in Candida albicans exerting antifungal and antibiofilm effects

Valderrama, Victoria; Sánchez, Paula; Delso, Macarena; Díaz-Dosque, Mario; Escobar, Alejandro; Budini, Mauricio; Catalán, Mabel; Vivar, Raúl; López-Muñoz, Rodrigo; Jara, José Antonio; Molina-Berríos, Alfredo

Keywords: Candida albicans, biofilm, mitochondria, antifungal, antibiofilm

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 Candida albicans reference strains (ATCC 90029 and ATCC 10231). Methods and results First, we determined minimal inhibitory concentration (MIC) using a microdilution assay. Both compounds exerted antifungal effects, and their 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%–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.

Más información

Título de la Revista: JOURNAL OF APPLIED MICROBIOLOGY
Volumen: 135
Número: 1
Editorial: Oxford University Press
Fecha de publicación: 2024
Página de inicio: 1
Página final: 9
Idioma: inglés
URL: https://academic.oup.com/jambio/article/135/1/lxad316/7499734?login=true
DOI:

https://doi.org/10.1093/jambio/lxad316

Notas: WOS core collection ISI