Discovery of a Novel Antifungal Agent in the Pathogen Box

ABSTRACT Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with ve...

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Autores principales:	François L. Mayer, James W. Kronstad
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	antifungal drug Candida albicans Cryptococcus gattii Cryptococcus neoformans Pathogen Box Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/217d8ba7035a4a5caea4d88acd988b93
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spelling	oai:doaj.org-article:217d8ba7035a4a5caea4d88acd988b932021-11-15T15:21:46ZDiscovery of a Novel Antifungal Agent in the Pathogen Box10.1128/mSphere.00120-172379-5042https://doaj.org/article/217d8ba7035a4a5caea4d88acd988b932017-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00120-17https://doaj.org/toc/2379-5042ABSTRACT Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with very high mortality rates. Patients with dysfunctional immune systems, such as individuals with HIV/AIDS, are particularly susceptible to fungal infections. Unfortunately, relatively few antifungal drugs are currently available and fungi frequently develop resistance, further complicating treatment approaches. In this study, we screened the Pathogen Box chemical library (Medicines for Malaria Venture, Switzerland) in an effort to identify novel antifungal compounds. This approach led to the discovery of a novel, highly potent antifungal agent with activity against both C. neoformans and C. albicans. Our initial study of the mechanism of action suggested that this novel compound prevents fungal proliferation by targeting the ability of C. neoformans to withstand stress at the plasma membrane and cell wall. Because this compound had previously been shown to have low toxicity for mammalian cells, we propose that it represents an attractive lead compound for further antifungal drug development. IMPORTANCE Cryptococcus neoformans and Candida albicans are two major human fungal pathogens and together account for over 1.4 million infections annually, with very high mortality rates. These fungi often infect immunocompromised individuals, such as HIV/AIDS patients. In an effort to identify novel drugs with antifungal activity, we have screened the Pathogen Box for compounds with anticryptococcal and anticandidal activities. This approach led to the discovery of a promising lead compound (MMV688271) with strong antifungal potency under nutrient-limited conditions.François L. MayerJames W. KronstadAmerican Society for Microbiologyarticleantifungal drugCandida albicansCryptococcus gattiiCryptococcus neoformansPathogen BoxMicrobiologyQR1-502ENmSphere, Vol 2, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	antifungal drug Candida albicans Cryptococcus gattii Cryptococcus neoformans Pathogen Box Microbiology QR1-502
spellingShingle	antifungal drug Candida albicans Cryptococcus gattii Cryptococcus neoformans Pathogen Box Microbiology QR1-502 François L. Mayer James W. Kronstad Discovery of a Novel Antifungal Agent in the Pathogen Box
description	ABSTRACT Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with very high mortality rates. Patients with dysfunctional immune systems, such as individuals with HIV/AIDS, are particularly susceptible to fungal infections. Unfortunately, relatively few antifungal drugs are currently available and fungi frequently develop resistance, further complicating treatment approaches. In this study, we screened the Pathogen Box chemical library (Medicines for Malaria Venture, Switzerland) in an effort to identify novel antifungal compounds. This approach led to the discovery of a novel, highly potent antifungal agent with activity against both C. neoformans and C. albicans. Our initial study of the mechanism of action suggested that this novel compound prevents fungal proliferation by targeting the ability of C. neoformans to withstand stress at the plasma membrane and cell wall. Because this compound had previously been shown to have low toxicity for mammalian cells, we propose that it represents an attractive lead compound for further antifungal drug development. IMPORTANCE Cryptococcus neoformans and Candida albicans are two major human fungal pathogens and together account for over 1.4 million infections annually, with very high mortality rates. These fungi often infect immunocompromised individuals, such as HIV/AIDS patients. In an effort to identify novel drugs with antifungal activity, we have screened the Pathogen Box for compounds with anticryptococcal and anticandidal activities. This approach led to the discovery of a promising lead compound (MMV688271) with strong antifungal potency under nutrient-limited conditions.
format	article
author	François L. Mayer James W. Kronstad
author_facet	François L. Mayer James W. Kronstad
author_sort	François L. Mayer
title	Discovery of a Novel Antifungal Agent in the Pathogen Box
title_short	Discovery of a Novel Antifungal Agent in the Pathogen Box
title_full	Discovery of a Novel Antifungal Agent in the Pathogen Box
title_fullStr	Discovery of a Novel Antifungal Agent in the Pathogen Box
title_full_unstemmed	Discovery of a Novel Antifungal Agent in the Pathogen Box
title_sort	discovery of a novel antifungal agent in the pathogen box
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/217d8ba7035a4a5caea4d88acd988b93
work_keys_str_mv	AT francoislmayer discoveryofanovelantifungalagentinthepathogenbox AT jameswkronstad discoveryofanovelantifungalagentinthepathogenbox
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Discovery of a Novel Antifungal Agent in the Pathogen Box

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