Antifungal activity of indolicidin-derived peptide In-58 against Sporothrix globosa in vitro and in vivo

In-58, a peptide derived from indolicidin, shows extraordinary antibacterial activity and lower toxicity than indolicidin toward mammalian cells. Here, we investigated the antifungal activity of In-58 against the human pathogen <i>Sporothrix globosa in vitro</i> and <i>in vivo</i>. In-58 markedly inhibited the growth of <i>Sporothrix globosa</i> isolates in microdilution assays and showed no antagonism with any tested antifungal agent (itraconazole, terbinafine or amphotericin B). Scanning electron microscopy and propidium iodide staining indicated that In-58 alters the cell wall integrity and interacts with DNA, leading to disruption of <i>S. globosa</i> in a dose-dependent manner. In <i>S. globosa</i>, the mitochondrial membrane potential decreased and reactive oxygen species increased after treatment with In-58. <i>In vivo</i> experiments in the <i>Galleria mellonella</i> (greater wax moth) larval infection model revealed the effectiveness of In-58 against <i>S. globosa</i> infection with low toxicity. Our results indicate that In-58 possesses remarkable antifungal activity against <i>S. globosa in vitro</i> and <i>in vivo</i>. It has potential as a novel drug for the treatment of sporotrichosis.