An immunomodulatory peptide that confers protection in an experimental candidemia murine model [PublishAheadOfPrint]

Fungal Candida species are commensals present in the mammalian skin and mucous membranes. Candida spp. are capable of breaching the epithelial barrier of immuno-compromised patients with neutrophil and cell-mediated immune dysfunctions, and it can also disseminate to multiple organs through the bloodstream. Here we examined the action of innate defence regulator (IDR)-1018, a 12-aminoacid residue peptide derived from bovine bactenecin (Bac2A), showed weak antifungal and anti-biofilm activity against C. albicans laboratory (ATCC 10231) and a clinical isolate (CI) strains (MICs of 32 μg.mL^-1 and 64 μg.mL^-1, respectively), while 8-fold lower concentrations led to dissolution of the fungal cells from pre-formed biofilms. IDR-1018 at 128 μg.mL^-1 was not hemolytic when tested against murine red blood cells, and also has not shown cytotoxic effect on murine monocyte RAW 264.7 and primary murine macrophage cells at the tested concentrations. IDR-1018 modulated the cytokine profile due to the challenge of murine bone marrow-derived macrophages when challenged with heat-killed C. albicans antigens (HKCA) by increasing MCP-1 and IL-10 levels, while suppressing TNF-α, IL-1β, IL-6, and IL-12 levels. Mice treated with IDR-1018 at 10 mg.kg^-1 had an increased survival rate in candidemia model when compared with PBS-treated mice, together with a diminished kidney fungal burden. Thus, IDR-1018 was able to protect against murine experimental candidemia and has the potential as an adjunctive therapy.

http://ift.tt/2sba7p4