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A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection

Disseminated infection by Candida species represents a common, often life-threatening condition. Increased resistance to current antifungal drugs has led to an urgent need to develop new antifungal drugs to treat this pathogen. However, in vivo screening of candidate antifungal compounds requires la...

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Autores principales: Ryan, Lisa K., Hise, Amy G, Hossain, Chowdhury Mobaswar, Ruddick, William, Parveen, Rezwana, Freeman, Katie B., Weaver, Damian G., Narra, Hema P., Scott, Richard W., Diamond, Gill
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712810/
https://www.ncbi.nlm.nih.gov/pubmed/33007818
http://dx.doi.org/10.3390/jof6040197
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author Ryan, Lisa K.
Hise, Amy G
Hossain, Chowdhury Mobaswar
Ruddick, William
Parveen, Rezwana
Freeman, Katie B.
Weaver, Damian G.
Narra, Hema P.
Scott, Richard W.
Diamond, Gill
author_facet Ryan, Lisa K.
Hise, Amy G
Hossain, Chowdhury Mobaswar
Ruddick, William
Parveen, Rezwana
Freeman, Katie B.
Weaver, Damian G.
Narra, Hema P.
Scott, Richard W.
Diamond, Gill
author_sort Ryan, Lisa K.
collection PubMed
description Disseminated infection by Candida species represents a common, often life-threatening condition. Increased resistance to current antifungal drugs has led to an urgent need to develop new antifungal drugs to treat this pathogen. However, in vivo screening of candidate antifungal compounds requires large numbers of animals and using immunosuppressive agents to allow for fungal dissemination. To increase the efficiency of screening, to use fewer mice, and to remove the need for immunosuppressive agents, which may interfere with the drug candidates, we tested the potential for a novel approach using in vivo imaging of a fluorescent strain of Candida albicans, in a mouse strain deficient in the host defense peptide, murine β-defensin 1 (mBD-1). We developed a strain of C. albicans that expresses red fluorescent protein (RFP), which exhibits similar infectivity to the non-fluorescent parent strain. When this strain was injected into immunocompetent mBD-1-deficient mice, we observed a non-lethal disseminated infection. Further, we could quantify its dissemination in real time, and observe the activity of an antifungal peptide mimetic drug by in vivo imaging. This novel method will allow for the rapid in vivo screening of antifungal drugs, using fewer mice, and increase the efficiency of testing new antifungal agents.
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spelling pubmed-77128102020-12-04 A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection Ryan, Lisa K. Hise, Amy G Hossain, Chowdhury Mobaswar Ruddick, William Parveen, Rezwana Freeman, Katie B. Weaver, Damian G. Narra, Hema P. Scott, Richard W. Diamond, Gill J Fungi (Basel) Article Disseminated infection by Candida species represents a common, often life-threatening condition. Increased resistance to current antifungal drugs has led to an urgent need to develop new antifungal drugs to treat this pathogen. However, in vivo screening of candidate antifungal compounds requires large numbers of animals and using immunosuppressive agents to allow for fungal dissemination. To increase the efficiency of screening, to use fewer mice, and to remove the need for immunosuppressive agents, which may interfere with the drug candidates, we tested the potential for a novel approach using in vivo imaging of a fluorescent strain of Candida albicans, in a mouse strain deficient in the host defense peptide, murine β-defensin 1 (mBD-1). We developed a strain of C. albicans that expresses red fluorescent protein (RFP), which exhibits similar infectivity to the non-fluorescent parent strain. When this strain was injected into immunocompetent mBD-1-deficient mice, we observed a non-lethal disseminated infection. Further, we could quantify its dissemination in real time, and observe the activity of an antifungal peptide mimetic drug by in vivo imaging. This novel method will allow for the rapid in vivo screening of antifungal drugs, using fewer mice, and increase the efficiency of testing new antifungal agents. MDPI 2020-09-30 /pmc/articles/PMC7712810/ /pubmed/33007818 http://dx.doi.org/10.3390/jof6040197 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ryan, Lisa K.
Hise, Amy G
Hossain, Chowdhury Mobaswar
Ruddick, William
Parveen, Rezwana
Freeman, Katie B.
Weaver, Damian G.
Narra, Hema P.
Scott, Richard W.
Diamond, Gill
A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title_full A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title_fullStr A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title_full_unstemmed A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title_short A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection
title_sort novel immunocompetent mouse model for testing antifungal drugs against invasive candida albicans infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712810/
https://www.ncbi.nlm.nih.gov/pubmed/33007818
http://dx.doi.org/10.3390/jof6040197
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