Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target

ABSTRACT Candida albicans is a major cause of fungal infections, both superficial and invasive. The economic costs as well as consequences for patient welfare are substantial. Only a few treatment options are available due to the high resemblance between fungal targets and host molecules, as both ar...

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Autores principales:	Liesbeth Demuyser, Ilse Palmans, Paul Vandecruys, Patrick Van Dijck
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans antifungal agents drug targets riboflavin vitamin B2 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/92a5202fb9be49b9bcea9a88fd348dc0
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spelling	oai:doaj.org-article:92a5202fb9be49b9bcea9a88fd348dc02021-11-15T15:30:51ZMolecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target10.1128/mSphere.00714-202379-5042https://doaj.org/article/92a5202fb9be49b9bcea9a88fd348dc02020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00714-20https://doaj.org/toc/2379-5042ABSTRACT Candida albicans is a major cause of fungal infections, both superficial and invasive. The economic costs as well as consequences for patient welfare are substantial. Only a few treatment options are available due to the high resemblance between fungal targets and host molecules, as both are eukaryotes. Riboflavin is a yellow pigment, also termed vitamin B2. Unlike animals, fungi can synthesize this essential component themselves, thereby leading us to appreciate that targeting riboflavin production is a promising novel strategy against fungal infections. Here, we report that the GTP cyclohydrolase encoded by C. albicans RIB1 (CaRIB1) is essential and rate-limiting for production of riboflavin in the fungal pathogen. We confirm the high potential of CaRib1 as an antifungal drug target, as its deletion completely impairs in vivo infectibility by C. albicans in model systems. Furthermore, the stimulating effect of iron deprivation and PKA activation on riboflavin production seems to involve CaRib1 and the upstream transcription factor CaSef1. Gathering insights in the synthesis mechanism of riboflavin in pathogenic fungi, like C. albicans, will allow us to design a novel strategy and specifically target this process to combat fungal infections. IMPORTANCE Candida albicans is an important fungal pathogen causing common superficial infections as well as invasive diseases with an extremely high morbidity and mortality. Antifungal therapies are limited in efficiency and availability. In this research, we describe the regulation of riboflavin production in C. albicans. Since riboflavin biosynthesis is essential to this organism, we can appreciate that targeting it would be a promising new strategy to combat these fungal infections. We provide evidence that one particular enzyme in the production process, CaRib1, would be most promising as an antifungal drug target, as it plays a central role in regulation and proves to be essential in a mouse model of systemic infection.Liesbeth DemuyserIlse PalmansPaul VandecruysPatrick Van DijckAmerican Society for MicrobiologyarticleCandida albicansantifungal agentsdrug targetsriboflavinvitamin B2MicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans antifungal agents drug targets riboflavin vitamin B2 Microbiology QR1-502
spellingShingle	Candida albicans antifungal agents drug targets riboflavin vitamin B2 Microbiology QR1-502 Liesbeth Demuyser Ilse Palmans Paul Vandecruys Patrick Van Dijck Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
description	ABSTRACT Candida albicans is a major cause of fungal infections, both superficial and invasive. The economic costs as well as consequences for patient welfare are substantial. Only a few treatment options are available due to the high resemblance between fungal targets and host molecules, as both are eukaryotes. Riboflavin is a yellow pigment, also termed vitamin B2. Unlike animals, fungi can synthesize this essential component themselves, thereby leading us to appreciate that targeting riboflavin production is a promising novel strategy against fungal infections. Here, we report that the GTP cyclohydrolase encoded by C. albicans RIB1 (CaRIB1) is essential and rate-limiting for production of riboflavin in the fungal pathogen. We confirm the high potential of CaRib1 as an antifungal drug target, as its deletion completely impairs in vivo infectibility by C. albicans in model systems. Furthermore, the stimulating effect of iron deprivation and PKA activation on riboflavin production seems to involve CaRib1 and the upstream transcription factor CaSef1. Gathering insights in the synthesis mechanism of riboflavin in pathogenic fungi, like C. albicans, will allow us to design a novel strategy and specifically target this process to combat fungal infections. IMPORTANCE Candida albicans is an important fungal pathogen causing common superficial infections as well as invasive diseases with an extremely high morbidity and mortality. Antifungal therapies are limited in efficiency and availability. In this research, we describe the regulation of riboflavin production in C. albicans. Since riboflavin biosynthesis is essential to this organism, we can appreciate that targeting it would be a promising new strategy to combat these fungal infections. We provide evidence that one particular enzyme in the production process, CaRib1, would be most promising as an antifungal drug target, as it plays a central role in regulation and proves to be essential in a mouse model of systemic infection.
format	article
author	Liesbeth Demuyser Ilse Palmans Paul Vandecruys Patrick Van Dijck
author_facet	Liesbeth Demuyser Ilse Palmans Paul Vandecruys Patrick Van Dijck
author_sort	Liesbeth Demuyser
title	Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
title_short	Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
title_full	Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
title_fullStr	Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
title_full_unstemmed	Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target
title_sort	molecular elucidation of riboflavin production and regulation in <named-content content-type="genus-species">candida albicans</named-content>, toward a novel antifungal drug target
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/92a5202fb9be49b9bcea9a88fd348dc0
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Molecular Elucidation of Riboflavin Production and Regulation in <named-content content-type="genus-species">Candida albicans</named-content>, toward a Novel Antifungal Drug Target

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