The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation

ABSTRACT Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen Candida albicans regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in Saccharomyces cerevisiae regulates nitrogen sensing...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peter R. Flanagan, Ning-Ning Liu, Darren J. Fitzpatrick, Karsten Hokamp, Julia R. Köhler, Gary P. Moran
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Candida albicans TOR biofilm virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/184353d3886447f7843e966550bd1769
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:184353d3886447f7843e966550bd1769
record_format	dspace
spelling	oai:doaj.org-article:184353d3886447f7843e966550bd17692021-11-15T15:21:52ZThe <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation10.1128/mSphere.00477-172379-5042https://doaj.org/article/184353d3886447f7843e966550bd17692017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00477-17https://doaj.org/toc/2379-5042ABSTRACT Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen Candida albicans regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in Saccharomyces cerevisiae regulates nitrogen sensing and TORC1 activation. Here, we characterize the role of C. albicansGTR1 in TORC1 activation and compare it with the previously characterized GTPase Rhb1. A homozygous gtr1/gtr1 mutant exhibited impaired TORC1-mediated phosphorylation of ribosomal protein S6 and increased susceptibility to rapamycin. Overexpression of GTR1 impaired nitrogen starvation-induced filamentous growth, MEP2 expression, and growth in bovine serum albumin as the sole nitrogen source. Both GTR1 and RHB1 were shown to regulate genes involved in ribosome biogenesis, amino acid biosynthesis, and expression of biofilm growth-induced genes. The rhb1/rhb1 mutant exhibited a different pattern of expression of Sko1-regulated genes and increased susceptibility to Congo red and calcofluor white. The homozygous gtr1/gtr1 mutant exhibited enhanced flocculation phenotypes and, similar to the rhb1/rhb1 mutant, exhibited enhanced biofilm formation on plastic surfaces. In summary, Gtr1 and Rhb1 link nutrient sensing and biofilm formation and this connectivity may have evolved to enhance the competitiveness of C. albicans in niches where there is intense competition with other microbes for space and nutrients. IMPORTANCE Candida albicans is the major fungal pathogen of humans and is responsible for a wide range of infections, including life-threatening systemic infections in susceptible hosts. Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in this fungus, and components of this complex are under increased investigation as targets for new antifungal drugs. The present study characterized the role of GTR1, encoding a putative GTPase, in TORC1 activation. This study shows that GTR1 encodes a protein required for activation of TORC1 activity in response to amino acids and regulation of nitrogen starvation responses. GTR1 mutants show increased cell-cell adhesion and biofilm formation and increased expression of genes involved in these processes. This study demonstrates that starvation responses and biofilm formation are coregulated by GTR1 and suggests that these responses are linked to compete with the microbiome for space and nutrients.Peter R. FlanaganNing-Ning LiuDarren J. FitzpatrickKarsten HokampJulia R. KöhlerGary P. MoranAmerican Society for MicrobiologyarticleCandida albicansTORbiofilmvirulenceMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans TOR biofilm virulence Microbiology QR1-502
spellingShingle	Candida albicans TOR biofilm virulence Microbiology QR1-502 Peter R. Flanagan Ning-Ning Liu Darren J. Fitzpatrick Karsten Hokamp Julia R. Köhler Gary P. Moran The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
description	ABSTRACT Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen Candida albicans regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in Saccharomyces cerevisiae regulates nitrogen sensing and TORC1 activation. Here, we characterize the role of C. albicansGTR1 in TORC1 activation and compare it with the previously characterized GTPase Rhb1. A homozygous gtr1/gtr1 mutant exhibited impaired TORC1-mediated phosphorylation of ribosomal protein S6 and increased susceptibility to rapamycin. Overexpression of GTR1 impaired nitrogen starvation-induced filamentous growth, MEP2 expression, and growth in bovine serum albumin as the sole nitrogen source. Both GTR1 and RHB1 were shown to regulate genes involved in ribosome biogenesis, amino acid biosynthesis, and expression of biofilm growth-induced genes. The rhb1/rhb1 mutant exhibited a different pattern of expression of Sko1-regulated genes and increased susceptibility to Congo red and calcofluor white. The homozygous gtr1/gtr1 mutant exhibited enhanced flocculation phenotypes and, similar to the rhb1/rhb1 mutant, exhibited enhanced biofilm formation on plastic surfaces. In summary, Gtr1 and Rhb1 link nutrient sensing and biofilm formation and this connectivity may have evolved to enhance the competitiveness of C. albicans in niches where there is intense competition with other microbes for space and nutrients. IMPORTANCE Candida albicans is the major fungal pathogen of humans and is responsible for a wide range of infections, including life-threatening systemic infections in susceptible hosts. Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in this fungus, and components of this complex are under increased investigation as targets for new antifungal drugs. The present study characterized the role of GTR1, encoding a putative GTPase, in TORC1 activation. This study shows that GTR1 encodes a protein required for activation of TORC1 activity in response to amino acids and regulation of nitrogen starvation responses. GTR1 mutants show increased cell-cell adhesion and biofilm formation and increased expression of genes involved in these processes. This study demonstrates that starvation responses and biofilm formation are coregulated by GTR1 and suggests that these responses are linked to compete with the microbiome for space and nutrients.
format	article
author	Peter R. Flanagan Ning-Ning Liu Darren J. Fitzpatrick Karsten Hokamp Julia R. Köhler Gary P. Moran
author_facet	Peter R. Flanagan Ning-Ning Liu Darren J. Fitzpatrick Karsten Hokamp Julia R. Köhler Gary P. Moran
author_sort	Peter R. Flanagan
title	The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
title_short	The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
title_full	The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
title_fullStr	The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
title_full_unstemmed	The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation
title_sort	<named-content content-type="genus-species">candida albicans</named-content> tor-activating gtpases gtr1 and rhb1 coregulate starvation responses and biofilm formation
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/184353d3886447f7843e966550bd1769
work_keys_str_mv	AT peterrflanagan thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT ningningliu thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT darrenjfitzpatrick thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT karstenhokamp thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT juliarkohler thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT garypmoran thenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT peterrflanagan namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT ningningliu namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT darrenjfitzpatrick namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT karstenhokamp namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT juliarkohler namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation AT garypmoran namedcontentcontenttypegenusspeciescandidaalbicansnamedcontenttoractivatinggtpasesgtr1andrhb1coregulatestarvationresponsesandbiofilmformation
_version_	1718428055729340416

The <named-content content-type="genus-species">Candida albicans</named-content> TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation

Ejemplares similares