Abstract
In the last few decades, fungal infections, particularly nosocomial, increased all around the world. This increment stimulated the search for new antifungal agents, especially those derived from nature. Among natural products, those from marine sources have gained prominence in the last years. Purified phlorotannins extracts from three brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus) were screened for their antifungal activity against human pathogenic yeast and filamentous fungi. The purified phlorotannins extracts from the studied seaweeds displayed fungistatic and fungicidal activity against yeast and dermatophytes, respectively, pointing to their interest as anti-dermatophyte agent. C. albicans ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum and Trichophyton rubrum were the most susceptible among dermatophytes. Since the antifungal mechanism constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, the mechanism of action of purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides seem to act by affecting the ergosterol composition of the cell membrane of yeast and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall composition by reducing the levels of chitin. Phlorotannins also seem to affect the respiratory chain function, as all of the studied species significantly increased the activity of mitochondrial dehydrogenases and increased the incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis inhibited the dimorphic transition of Candida albicans, leading to the formation of pseudohyphae with diminished capacity to adhere to epithelial cells. This finding is associated with a decrease of C. albicans virulence and capacity to invade host cells and can be potentially interesting for combined antifungal therapy, namely for the control of invasive candidiasis.
Highlights
Resistance to antifungal agents has significantly increased over the past few decades
With the exception of M. gypseum, that was resistant to C. usneoides, all of the studied dermatophytes were sensitive to the purified phlorotannins extracts, with fungistatic and fungicidal activity
C. albicans is a commensal yeast which commonly colonizes the mucosa of the majority of healthy humans without causing tissue damage
Summary
Resistance to antifungal agents has significantly increased over the past few decades. Candida albicans and Trichophytom rubrum are among the most common fungal agents, frequently responsible for a variety of infections, ranging from superficial mycoses to life threatening systemic infections [1]. Both yeast and dermatophytes infections can become important causes of morbidity and mortality, especially among immunocompromised patients, with important implications in the health care costs of hospitals and communities [2]. An inevitable consequence of the increased use of antifungal agents in the past decades is the increment of the number and variety of fungal resistance. The study of antifungals’ mechanism of action constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, as well as to develop safer and more potent compounds in the future
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