Abstract

Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 μM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use.

Highlights

  • Oral candidiasis (OC) is one of the most common fungal infections affecting the oral cavity [1]

  • Susceptibility assay of lichochalcone-A against C. albicans (MYA2876) showed an antifungal activity, as indicated by the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of 62.5–150 μM and 150 μM; respectively, which were

  • Time-kill experiment showed the most decrease in fungal viability occurring in the first 5 hours after application of the lichochalcone-A treatment at 10x MIC (625 μM) and 20x MIC (1250 μM) to C. albicans (MYA 2876) inoculum (103 colony formation unit (CFU)/ml) (Fig 2)

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Summary

Objectives

The aims of the present study were to evaluate the antifungal activity of lichochalcone-A against C. albicans in vitro and to determine if lichochalcone-A can disrupt biofilm formation by reducing critical virulence factors associated with C. albicans, such as secretion of proteolytic enzymes, which are often implicated in the degradation of host mucosal tissue [3]

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Results
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