Sphingolipid Inhibitors as an Alternative to Treat Candidiasis Caused by Fluconazole-Resistant Strains

• Main Authors: Rodrigo Rollin-Pinheiro, Brayan Bayona-Pacheco, Levy Tenorio Sousa Domingos, Jose Alexandre da Rocha Curvelo, Gabriellen Menezes Migliani de Castro, Eliana Barreto-Bergter, Antonio Ferreira-Pereira
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Pathogens
• Subjects: <i>Candida</i>; sphingolipids; myriocin; fungal infections
• Online Access: https://www.mdpi.com/2076-0817/10/7/856

<i>Candida</i> species are fungal pathogens known to cause a wide spectrum of diseases, and <i>Candida albicans</i> and <i>Candida glabrata</i> are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant to fluconazole, the first choice of treatment for these infections. Fungal sphingolipids have been considered a potential target for new therapeutic approaches and some inhibitors have already been tested against pathogenic fungi. The present study therefore aimed to evaluate the action of two sphingolipid synthesis inhibitors, aureobasidin A and myriocin, against different <i>C. albicans</i> and <i>C. glabrata</i> strains, including clinical isolates resistant to fluconazole. Susceptibility tests of aureobasidin A and myriocin were performed using CLSI protocols, and their interaction with fluconazole was evaluated by a checkerboard protocol. All <i>Candida</i> strains tested were sensitive to both inhibitors. Regarding the evaluation of drug interaction, both aureobasidin A and myriocin were synergic with fluconazole, demonstrating that sphingolipid synthesis inhibition could enhance the effect of fluconazole. Thus, these results suggest that sphingolipid inhibitors in conjunction with fluconazole could be useful for treating candidiasis cases, especially those caused by fluconazole resistant isolates.