Antifungal Activity of Citral by Disruption of Ergosterol Biosynthesis in Fluconazole Resistant Candida tropicalis
Janiere Pereira de Sousa *
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Aratã Oliveira Cortez Costa
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Maria Clerya Alvino Leite
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Felipe Queiroga Sarmento Guerra
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Viviane Araújo da Silva
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Camilla Pinheiro de Menezes
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
Fillipe Oliveira Pereira
Education and Health Center, Federal University of Campina Grande, Cuité, Paraíba, Brazil.
Edeltrudes Oliveira Lima
Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, 58051-970, Brazil.
*Author to whom correspondence should be addressed.
Abstract
A limited number of antifungals and the emergence of resistant strains have hindered the treatment of candidiasis, making the search for new antifungals urgent. Citral is a monoterpene with known pharmacological properties, including antimicrobial action.
Aims: Thus the objective of this study was to investigate the possible mechanism of citral’s action against Candida tropicalis isolated from human blood, and the effect of its association with antifungals.
Methodology: The minimum inhibitory concentration (MIC), the minimum fungicidal concentration (MFC), the effect of citral on the cell wall (sorbitol assay), and membrane ergosterol binding were evaluated using broth microdilution technique. We also evaluated interference in ergosterol biosynthesis, and the citral-antifungal association effect (checkerboard method).
Results: The MIC90 and MFC90 of citral were respectively 512 and 1024 μg / mL. The MIC of citral did not increase when sorbitol or ergosterol was added to the medium, suggesting that citral does not act on the cell wall or by membrane ergosterol binding. However, citral inhibited ergosterol biosynthesis, and the citral-fluconazole combination showed synergistic effects for the ATCC strain. Conclusion: This study contributes to understanding the antifungal mechanism of citral’s action, and to the development of new therapies for candidiasis treatment.
Keywords: Mode of action, monoterpene, antifungal activity, candidiasis, ergosterol.