Abstract
Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections.
Highlights
Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis
We evaluated ToAP2 and non-disulfide-bridged peptides (NDBP)-5.7 Minimal inhibitory concentrations (MIC) for both C. albicans strains at a cell density of 1 × 106 cells/mL
We further evaluated the antifungal activity of two Antimicrobial peptides (AMPs) previously described and partially characterized by our group, ToAP2 and NDBP-5.7
Summary
Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization Both peptides showed synergism with amphotericin B, while ToAP2 presents a synergic effect with fluconazole. Many of the current systemic antifungal drugs are toxic to host cells often producing important side effects. These factors stress the need of new therapeutic strategies against candidiasis and other mycoses[20]. AMPs have been shown to be effective against bacteria, fungi, viruses and protozoa and are less prone to induce resistance because of their multiple cellular targets[34,35,36,37]
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