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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7712810 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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