An immunomodulatory peptide confers protection in an experimental candidemia murine model

Camila G. Freitas, Stella M.F. Lima, Mirna S. Freire, Ana Paula C. Cantuária, Nelson G.O. Júnior, Tatiane S. Santos, Jéssica S. Folha, Suzana M. Ribeiro, Simoni C. Dias, Taia M.B. Rezende, Patrícia Albuquerque, André M. Nicola, César De La Fuente-Núñez, Robert Hancock, Octávio L. Franco, Maria Sueli S. Felipe

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 heatkilled 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 phosphatebuffered 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.

LanguageEnglish
Article numbere02518
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Freitas, C. G., Lima, S. M. F., Freire, M. S., Cantuária, A. P. C., Júnior, N. G. O., Santos, T. S., ... Felipe, M. S. S. (2017). An immunomodulatory peptide confers protection in an experimental candidemia murine model. Antimicrobial Agents and Chemotherapy, 61(8), [e02518]. https://doi.org/10.1128/AAC.02518-16
Freitas, Camila G. ; Lima, Stella M.F. ; Freire, Mirna S. ; Cantuária, Ana Paula C. ; Júnior, Nelson G.O. ; Santos, Tatiane S. ; Folha, Jéssica S. ; Ribeiro, Suzana M. ; Dias, Simoni C. ; Rezende, Taia M.B. ; Albuquerque, Patrícia ; Nicola, André M. ; De La Fuente-Núñez, César ; Hancock, Robert ; Franco, Octávio L. ; Felipe, Maria Sueli S. / An immunomodulatory peptide confers protection in an experimental candidemia murine model. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 8.
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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 heatkilled 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 phosphatebuffered 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.",
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Freitas, CG, Lima, SMF, Freire, MS, Cantuária, APC, Júnior, NGO, Santos, TS, Folha, JS, Ribeiro, SM, Dias, SC, Rezende, TMB, Albuquerque, P, Nicola, AM, De La Fuente-Núñez, C, Hancock, R, Franco, OL & Felipe, MSS 2017, 'An immunomodulatory peptide confers protection in an experimental candidemia murine model', Antimicrobial Agents and Chemotherapy, vol. 61, no. 8, e02518. https://doi.org/10.1128/AAC.02518-16

An immunomodulatory peptide confers protection in an experimental candidemia murine model. / Freitas, Camila G.; Lima, Stella M.F.; Freire, Mirna S.; Cantuária, Ana Paula C.; Júnior, Nelson G.O.; Santos, Tatiane S.; Folha, Jéssica S.; Ribeiro, Suzana M.; Dias, Simoni C.; Rezende, Taia M.B.; Albuquerque, Patrícia; Nicola, André M.; De La Fuente-Núñez, César; Hancock, Robert; Franco, Octávio L.; Felipe, Maria Sueli S.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 8, e02518, 01.08.2017.

Research output: Contribution to journalArticle

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AU - Lima, Stella M.F.

AU - Freire, Mirna S.

AU - Cantuária, Ana Paula C.

AU - Júnior, Nelson G.O.

AU - Santos, Tatiane S.

AU - Folha, Jéssica S.

AU - Ribeiro, Suzana M.

AU - Dias, Simoni C.

AU - Rezende, Taia M.B.

AU - Albuquerque, Patrícia

AU - Nicola, André M.

AU - De La Fuente-Núñez, César

AU - Hancock, Robert

AU - Franco, Octávio L.

AU - Felipe, Maria Sueli S.

PY - 2017/8/1

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N2 - 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 heatkilled 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 phosphatebuffered 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.

AB - 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 heatkilled 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 phosphatebuffered 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.

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Freitas CG, Lima SMF, Freire MS, Cantuária APC, Júnior NGO, Santos TS et al. An immunomodulatory peptide confers protection in an experimental candidemia murine model. Antimicrobial Agents and Chemotherapy. 2017 Aug 1;61(8). e02518. https://doi.org/10.1128/AAC.02518-16