Candida species are one of the most concerning causative agents of
fungal infections in humans. The treatment of invasive
Candida infections is based on the use of
fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity.
Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the
sphingolipid biosynthetic pathway have been described to display antifungal properties, such as
myriocin and
aureobasidin A, which are active against resistant Candida isolates. In the present study,
aureobasidin A did not display antibiofilm activity nor synergism with
amphotericin B, but its combination with
fluconazole was effective against Candida biofilms and protected the host in an in vivo
infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and
chitin content, as well as altered morphology, enhanced
DNA leakage and a greater susceptibility to
sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of
aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of Candida species.