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Planta Med 2017; 83(03/04): 326-333
DOI: 10.1055/s-0042-116442
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Usnic Acid Activity on Oxidative and Nitrosative Stress of Azole-Resistant Candida albicans Biofilm

Mariana Andrea Peralta
1   Instituto Multidisciplinario de Biología Vegetal (IMBIV) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina
,
María Angel da Silva
2   Instituto Multidisciplinario de Biología Vegetal (IMBIV) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Cátedra de Microbiología, Facultad de Ciencias Exactas Físicas y Naturales. Universidad Nacional de Córdoba, Argentina
,
María Gabriela Ortega
1   Instituto Multidisciplinario de Biología Vegetal (IMBIV) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina
,
José Luis Cabrera
1   Instituto Multidisciplinario de Biología Vegetal (IMBIV) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina
,
María Gabriela Paraje
2   Instituto Multidisciplinario de Biología Vegetal (IMBIV) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Cátedra de Microbiología, Facultad de Ciencias Exactas Físicas y Naturales. Universidad Nacional de Córdoba, Argentina
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Further Information

Publication History

received 28 April 2016
revised 18 August 2016

accepted 29 August 2016

Publication Date:
20 September 2016 (online)

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Abstract

Several studies report that (+)-usnic acid, a lichen secondary metabolite, inhibits growth of different bacteria and fungi; however, the mechanism of its antimicrobial activity remains unknown. In this study, we explored the ability of usnic acid, obtained from Usnea amblyoclada, as an antibiofilm agent against azole-resistant and azole-sensitive Candida albicans strains by studying the cellular stress and antioxidant response in biofilms. The biofilm inhibitory concentration of usnic acid (4 µg/mL) exhibited a significant biofilm inhibition, 71.08 % for azole-resistant and 87.84 % for azole-sensitive C. albicans strains. Confocal scanning laser microscopy showed that the morphology of mature biofilm was altered (reduced the biomass and thickness) in the presence of usnic acid. The antifungal effect was mediated by an oxidative and nitrosative stress, with a significant accumulation of intracellular and extracellular reactive oxygen species detected by confocal scanning laser microscopy and by nitro blue tetrazolium, respectively. In fact, azole-resistant and azole-sensitive C. albicans biofilms treated at the biofilm inhibitory concentration of usnic acid presented 30-fold and 10-fold increased reactive oxygen species measurements compared to basal levels, respectively, and important nitric oxide generation, showing 25-fold and 60-fold increased reactive nitrogen intermediates levels with respect to the controls, respectively. Nonenzymatic and enzymatic antioxidant defenses were increased in both strains compared to biofilm basal levels as response to the increase of oxidant metabolites. The present study shows for the first time that usnic acid can alter the prooxidant-antioxidant balance, which may be the cause of the irreversible cell damage and lead to cell death. Our results suggest that usnic acid could be an alternative for the treatment of Candida infections, which deserves further investigation.

Key words

Usnea amblyoclada - Usneaceae - usnic acid - Candida albicans - biofilms - prooxidant-antioxidant balance

Supporting Information

 

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