Zerumbone use to enhance the photodynamic inactivation of CANDIDA ALBICANS biofilm: assessment in clinically fluconazole-resistant isolates and in a murine model of oral candidiasis

• Grant number: 24/00741-5
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2024
• End date: October 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ana Cláudia Pavarina
• Grantee: Ana Cláudia Pavarina
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Antifungal resistance to conventional drugs has been a challenge in controlling fungal infections. Approaches that reduce extracellular polymeric substances weaken the biofilm structure, making it more susceptible to the action of antifungal therapies. Antimicrobial photodynamic therapy (aPDT) has been investigated for the control of Candida albicans biofilms and present promising results in the reduction of the biofilm of fluconazole-susceptible strain, however, fluconazole-resistant strains have reduced susceptibility to aPDT. In a previous study, it was observed that Zerumbone (ZER) reduced cell viability and components of the extracellular matrix of fluconazole-susceptible (CaS) and fluconazole-resistant (CaR) C. albicans biofilms, being a promising alternative for antifungal therapies. In this context, the present study will be conducted to evaluate the viability of using of ZER associated with aPDT in the inactivation of fluconazole-resistant C. albicans isolates and in the treatment of oral candidosis induced in mice contaminated with CaS and CaR strains. This project will be conducted into three stages: Objective I) Will be evaluate the efficacy of ZER associated with aPDT (mediated by PDZ associated with LED light), in CaS (ATCC) and CaR biofilms [ATCC and clinical isolates (R14 and R70)] with a focus on reducing of the fungal population and components from the extracellular matrix of the biofilm [water-soluble polysaccharides (WSP), alkali-soluble polysaccharides (ASP), extracellular DNA (eDNA), proteins and biomass (total and insoluble)]; Objective II): Will be evaluate the cytotoxic effect of the association of ZER with aPDT on human cells (NOK-si and FGH) in a 3D co-culture model infected with CaS and CaR; and, Objective III: Will be evaluate whether the application of ZER enhances the action of aPDT in the treatment of oral candidosis induced in mice infected with CaS and CaR strains, focusing on the recovery of the viable fungal population and resolution of lesions on the animals' tongue. In addition to the microbiological evaluation, macroscopic and histological analysis of the lesions will also be carried out. Confocal Laser Microscopy techniques will be used to mark the 3D structure of components of the biofilm matrix. All in vitro experiments will be carried out in quadruplicate, on 3 separate occasions (n=12). In the in vivo study, seven animals will be used for each experimental condition, except the CNI+ (n = 3) and CNI- (n=3) groups. The most appropriate statistical test will be applied respecting the assumptions established in the experimental design, considering a significance level of 5% (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ABREU-PEREIRA, CESAR AUGUSTO; GORAYB-PEREIRA, ANA LUIZA; JORDA, CLAUDIA CAROLINA; PARO, CLARA BRAIT; BARBUGLI, PAULA ABOUD; PAVARINA, ANA CLAUDIA. Zerumbone enhances the photodynamic effect against biofilms of fluconazole-resistant Candida albicans clinical isolates. Journal of Dentistry, v. 155, p. 10-pg., 2025-04-01. (24/00741-5, 13/07276-1)