Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT The zinc cluster transcription factor Put3 was initially characterized in Saccharomyces cerevisiae as the transcriptional activator of PUT1 and PUT2, two genes acting early in the proline assimilation pathway. We have used phenotypic studies, transcription profiling, and chromatin immunopre...

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Autores principales:	Walters Aji Tebung, Raha Parvizi Omran, Debra L. Fulton, Joachim Morschhäuser, Malcolm Whiteway
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Candida albicans Put3 Put3 regulation Saccharomyces cerevisiae carbon source nitrogen source Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/77186ece3bef45f6a723ff611d61aa39
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spelling	oai:doaj.org-article:77186ece3bef45f6a723ff611d61aa392021-11-15T15:21:53ZPut3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mSphere.00354-172379-5042https://doaj.org/article/77186ece3bef45f6a723ff611d61aa392017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00354-17https://doaj.org/toc/2379-5042ABSTRACT The zinc cluster transcription factor Put3 was initially characterized in Saccharomyces cerevisiae as the transcriptional activator of PUT1 and PUT2, two genes acting early in the proline assimilation pathway. We have used phenotypic studies, transcription profiling, and chromatin immunoprecipitation with microarray technology (ChIP-chip) to establish that unlike S. cerevisiae, which only uses proline as a nitrogen source, Candida albicans can use proline as a nitrogen source, a carbon source, or a source of both nitrogen and carbon. However, a C. albicansput3 null mutant cannot grow on proline, suggesting that as in S. cerevisiae, C. albicans Put3 (CaPut3) is required for proline catabolism, and because the C. albicansput3 null mutant grew efficiently on glutamate as the sole carbon or nitrogen source, it appears that CaPut3 also regulates the early genes of the pathway. CaPut3 showed direct binding to the CaPUT1 promoter, and both PUT1 and PUT2 were upregulated in response to proline addition in a Put3-dependent manner, as well as in a C. albicans strain expressing a hyperactive Put3. CaPut3 directs proline degradation even in the presence of a good nitrogen source such as ammonia, which contrasts with S. cerevisiae Put3 (ScPut3)-regulated proline catabolism, which only occurs in the absence of a rich nitrogen source. Thus, while overall proline regulatory circuitry differs between S. cerevisiae and C. albicans, the specific role of Put3 appears fundamentally conserved. IMPORTANCE Candida albicans poses a significant threat to the lives of immunocompromised people. Historically, knowledge has been drawn from studies on Saccharomyces cerevisiae to understand the pathogen, and many Candida albicans genes are named after their S. cerevisiae orthologs. Direct studies on the pathogen have, however, revealed differences in the roles of some orthologous proteins in the two yeasts. We show that the Put3 transcription factor allows the pathogen to completely degrade proline to usable nitrogen and carbon by evading regulatory restrictions imposed on its S. cerevisiae ortholog, which mandates conditional use of proline only as a nitrogen source in the baker’s yeast. The ability of Candida albicans to freely obtain nutrients from multiple sources may help it thrive as a commensal and opportunistic pathogen.Walters Aji TebungRaha Parvizi OmranDebra L. FultonJoachim MorschhäuserMalcolm WhitewayAmerican Society for MicrobiologyarticleCandida albicansPut3Put3 regulationSaccharomyces cerevisiaecarbon sourcenitrogen sourceMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Put3 Put3 regulation Saccharomyces cerevisiae carbon source nitrogen source Microbiology QR1-502
spellingShingle	Candida albicans Put3 Put3 regulation Saccharomyces cerevisiae carbon source nitrogen source Microbiology QR1-502 Walters Aji Tebung Raha Parvizi Omran Debra L. Fulton Joachim Morschhäuser Malcolm Whiteway Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT The zinc cluster transcription factor Put3 was initially characterized in Saccharomyces cerevisiae as the transcriptional activator of PUT1 and PUT2, two genes acting early in the proline assimilation pathway. We have used phenotypic studies, transcription profiling, and chromatin immunoprecipitation with microarray technology (ChIP-chip) to establish that unlike S. cerevisiae, which only uses proline as a nitrogen source, Candida albicans can use proline as a nitrogen source, a carbon source, or a source of both nitrogen and carbon. However, a C. albicansput3 null mutant cannot grow on proline, suggesting that as in S. cerevisiae, C. albicans Put3 (CaPut3) is required for proline catabolism, and because the C. albicansput3 null mutant grew efficiently on glutamate as the sole carbon or nitrogen source, it appears that CaPut3 also regulates the early genes of the pathway. CaPut3 showed direct binding to the CaPUT1 promoter, and both PUT1 and PUT2 were upregulated in response to proline addition in a Put3-dependent manner, as well as in a C. albicans strain expressing a hyperactive Put3. CaPut3 directs proline degradation even in the presence of a good nitrogen source such as ammonia, which contrasts with S. cerevisiae Put3 (ScPut3)-regulated proline catabolism, which only occurs in the absence of a rich nitrogen source. Thus, while overall proline regulatory circuitry differs between S. cerevisiae and C. albicans, the specific role of Put3 appears fundamentally conserved. IMPORTANCE Candida albicans poses a significant threat to the lives of immunocompromised people. Historically, knowledge has been drawn from studies on Saccharomyces cerevisiae to understand the pathogen, and many Candida albicans genes are named after their S. cerevisiae orthologs. Direct studies on the pathogen have, however, revealed differences in the roles of some orthologous proteins in the two yeasts. We show that the Put3 transcription factor allows the pathogen to completely degrade proline to usable nitrogen and carbon by evading regulatory restrictions imposed on its S. cerevisiae ortholog, which mandates conditional use of proline only as a nitrogen source in the baker’s yeast. The ability of Candida albicans to freely obtain nutrients from multiple sources may help it thrive as a commensal and opportunistic pathogen.
format	article
author	Walters Aji Tebung Raha Parvizi Omran Debra L. Fulton Joachim Morschhäuser Malcolm Whiteway
author_facet	Walters Aji Tebung Raha Parvizi Omran Debra L. Fulton Joachim Morschhäuser Malcolm Whiteway
author_sort	Walters Aji Tebung
title	Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
title_short	Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
title_full	Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	put3 positively regulates proline utilization in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/77186ece3bef45f6a723ff611d61aa39
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Put3 Positively Regulates Proline Utilization in <named-content content-type="genus-species">Candida albicans</named-content>

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