The Mechanism Of Vma11 Mediated Oral Candidiasis And Targeted Therapy
Year: 2025
Type: article
Abstract: Aim or purpose There is an urgent need to identify novel antifungal targets and elucidate their functional mechanisms for Candida albicans mediated oral mucosal infections. The V0c' subunit encoded by VMA11 of C. albicans vacuolar proton pump (V-ATPase) has no mammalian homolog, making it a potential target for antifungi. This study aims to investigate the role and mechanism of VMA11 in oral candidiasis and screen compounds targeting V0c' subunit, thereby suppressing C. albicans mediated oral mucosal infection. Materials and methods To investigate the impact of VMA11 on C. albicans virulence, assessing its role and mechanisms on epithelial infection in vitro and in vivo. Screening compounds target V0c' subunit, followed by experimental validation of its effect on C. albicans virulence. Results VMA11 regulated hyphal formation of C. albicans through MAPK and cAMP-PKA pathways. The VMA11 knockout strain exhibited impaired ability to damage oral epithelial cells. Transcriptome analysis revealed downregulation of inflammatory signaling pathways (including MAPK, PI3K-Akt, and IL-17) in epithelial cells infected with the VMA11 knockout strain. Compared with wild type, the deletion of VMA11 failed to form characteristic white patches on murine tongue surfaces and showed neither hyphal invasion nor inflammatory infiltration. The compound N026 (200 μg/mL) significantly inhibited hyphal growth and biofilm formation of both wild type and clinically resistant strain, reducing C. albicans adhesion and damage on oral epithelial cells. Conclusions VMA11 regulates hyphal formation and virulence of C. albicans through MAPK and cAMP-PKA signaling pathways. Compound N026 targeted V0c' subunit can inhibit C. albicans hyphal formation and oral candidiasis.
Source: International Dental Journal
Authors: Wang Zheng, Yang Deqin
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,550
OpenAlex ID: W4415831132
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