Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.

Язык: Английский

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In vitro and in vivo activity of 1,2,3,4,6-O-pentagalloyl-glucose against Candida albicans

Antimicrobial Agents and Chemotherapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

ABSTRACT Invasive fungal infections have become an increasingly serious threat to global human health, underscoring the urgent need for development of new antifungal drugs. In this study, we found a natural polyphenolic compound 1,2,3,4,6-O-pentagalloyl-glucose (PGG), which is present in various plants and herbs. PGG showed broad-spectrum activities, enhancing efficacy fluconazole. Furthermore, could protect mice against gastrointestinal systemic infection with Candida albicans . Our mechanistic studies revealed that exerts its effects partially by binding CaEno1 protein inhibit activity. As crucial therapeutic target, Eno1 has been reported be closely associated cancer, hypertension, infectious diseases. findings indicated PGG, inhibitor, potential candidate further development.

Язык: Английский

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Integrating ensemble machine learning and multi-omics approaches to identify Dp44mT as a novel anti-Candida albicans agent targeting cellular iron homeostasis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 24, 2025

Introduction Candidiasis, mainly caused by Candida albicans , poses a serious threat to human health. The escalating drug resistance in C. and the limited antifungal options highlight critical need for novel therapeutic strategies. Methods We evaluated 12 machine learning models on self-constructed dataset with known anti- activity. Based their performance, optimal model was selected screen our separate in-house compound library unknown activity potential agents. of compounds confirmed through vitro susceptibility assays, hyphal growth biofilm formation assays. Through transcriptomics, proteomics, iron rescue experiments, CTC staining, JC-1 DAPI molecular docking, dynamics simulations, we elucidated mechanism underlying compound. Result Among models, best predictive an ensemble constructed from Random Forests Categorical Boosting using soft voting. It predicts that Dp44mT exhibits potent tests further verified this finding can inhibit planktonic growth, formation, . Mechanistically, exerts disrupting cellular homeostasis, leading collapse mitochondrial membrane ultimately causing apoptosis. Conclusion This study presents practical approach predicting com-pounds provides new insights into development homeostasis

Язык: Английский

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Extracellular Hsp90 of Candida albicans contributes to the virulence of the pathogen by activating the NF-κB signaling pathway and inducing macrophage pyroptosis

Microbiological Research, Год журнала: 2024, Номер 290, С. 127964 - 127964

Опубликована: Ноя. 5, 2024

Язык: Английский

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