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An Immunomodulatory Peptide Confers Protection in an Experimental Candidemia Murine Model

2017; American Society for Microbiology; Volume: 61; Issue: 8 Linguagem: Inglês

10.1128/aac.02518-16

1098-6596

Camila Guimarães de Freitas, Stella Maris de Freitas Lima, Mirna S. Freire, Ana Paula de Castro Cantuária, Nelson G. Oliveira-Júnior, Tatiane Siqueira dos Santos, Jéssica S. Folha, Suzana M. Ribeiro, Simoni Campos Dias, Taia Maria Berto Rezende, Patrícia Albuquerque, André Moraes Nicola, César de la Fuente‐Núñez, Robert E. W. Hancock, Octávio Luiz Franco, Maria Sueli Soares Felipe,

Fungal Infections and Studies

ABSTRACT Fungal Candida species are commensals present in the mammalian skin and mucous membranes. Candida spp. are capable of breaching the epithelial barrier of immunocompromised patients with neutrophil and cell-mediated immune dysfunctions and can also disseminate to multiple organs through the bloodstream. Here we examined the action of innate defense regulator 1018 (IDR-1018), a 12-amino-acid-residue peptide derived from bovine bactenecin (Bac2A): IDR-1018 showed weak antifungal and antibiofilm activity against a Candida albicans laboratory strain (ATCC 10231) and a clinical isolate (CI) (MICs of 32 and 64 μg · ml −1 , respectively), while 8-fold lower concentrations led to dissolution of the fungal cells from preformed biofilms. IDR-1018 at 128 μg · ml −1 was not hemolytic when tested against murine red blood cells and also has not shown a cytotoxic effect on murine monocyte RAW 264.7 and primary murine macrophage cells at the tested concentrations. IDR-1018 modulated the cytokine profile during challenge of murine bone marrow-derived macrophages with heat-killed C. albicans (HKCA) antigens by increasing monocyte chemoattractant protein 1 (MCP-1) and interleukin-10 (IL-10) levels, while suppressing tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, and IL-12 levels. Mice treated with IDR-1018 at 10 mg · kg −1 of body weight had an increased survival rate in the candidemia model compared with phosphate-buffered saline (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.