Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT Candida albicans is an opportunistic, dimorphic fungus that causes candidiasis in immunocompromised people. C. albicans forms specialized structures called microcolonies that are important for surface adhesion and virulence. Microcolonies form in response to specific environmental condition...

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Autores principales:	Rohitashw Kumar, Malabika Maulik, Ruvini U. Pathirana, Paul J. Cullen, Mira Edgerton
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans Ras1-cAMP Sho1 glycolysis microcolonies Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1337f62bf57946ed89116615b43729a5
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spelling	oai:doaj.org-article:1337f62bf57946ed89116615b43729a52021-11-15T15:30:51ZSho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mSphere.00366-202379-5042https://doaj.org/article/1337f62bf57946ed89116615b43729a52020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00366-20https://doaj.org/toc/2379-5042ABSTRACT Candida albicans is an opportunistic, dimorphic fungus that causes candidiasis in immunocompromised people. C. albicans forms specialized structures called microcolonies that are important for surface adhesion and virulence. Microcolonies form in response to specific environmental conditions and require glycolytic substrates for optimal growth. However, fungal signaling pathways involved in sensing and transmitting these environmental cues to induce microcolony formation have not been identified. Here, we show that the C. albicans Ras1-cAMP cascade is required for microcolony formation, while the Cek1-MAP kinase pathway is not required, and Hog1 represses microcolony formation. The membrane protein Sho1, known to regulate the Cek1 pathway in yeasts, was indispensable for C. albicans microcolony formation but regulated the Ras1-cAMP pathway instead, based upon diminished intracellular levels of cAMP and reduced expression of core microcolony genes, including HWP1, PGA10, and ECE1, in C. albicans sho1Δ cells. Based upon predicted physical interactions between Sho1 and the glycolytic enzymes Pfk1, Fba1, Pgk1, and Cdc19, we hypothesized that Sho1 regulates Ras1-cAMP by establishing cellular energy levels produced by glycolysis. Indeed, microcolony formation was restored in C. albicans sho1Δ cells by addition of exogenous intermediates of glycolysis, including downstream products of each predicted interacting enzyme (fructose 1,6 bisphosphate, glyceraldehyde phosphate, 3-phosphoglyceric acid, and pyruvate). Thus, C. albicans Sho1 is an upstream regulator of the Ras1-cAMP signaling pathway that connects glycolytic metabolism to the formation of pathogenic microcolonies. IMPORTANCE C. albicans microcolonies form extensive hyphal structures that enhance surface adherence and penetrate underlying tissues to promote fungal infections. This study examined the environmental conditions that promote microcolony formation and how these signals are relayed, in order to disrupt signaling and reduce pathogenesis. We found that a membrane-localized protein, Sho1, is an upstream regulator of glycolysis and required for Ras1-cAMP signaling. Sho1 controlled the Ras1-dependent expression of core microcolony genes involved in adhesion and virulence. This new regulatory function for Sho1 linking glycolysis to microcolony formation reveals a novel role for this fungal membrane protein.Rohitashw KumarMalabika MaulikRuvini U. PathiranaPaul J. CullenMira EdgertonAmerican Society for MicrobiologyarticleCandida albicansRas1-cAMPSho1glycolysismicrocoloniesMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Ras1-cAMP Sho1 glycolysis microcolonies Microbiology QR1-502
spellingShingle	Candida albicans Ras1-cAMP Sho1 glycolysis microcolonies Microbiology QR1-502 Rohitashw Kumar Malabika Maulik Ruvini U. Pathirana Paul J. Cullen Mira Edgerton Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT Candida albicans is an opportunistic, dimorphic fungus that causes candidiasis in immunocompromised people. C. albicans forms specialized structures called microcolonies that are important for surface adhesion and virulence. Microcolonies form in response to specific environmental conditions and require glycolytic substrates for optimal growth. However, fungal signaling pathways involved in sensing and transmitting these environmental cues to induce microcolony formation have not been identified. Here, we show that the C. albicans Ras1-cAMP cascade is required for microcolony formation, while the Cek1-MAP kinase pathway is not required, and Hog1 represses microcolony formation. The membrane protein Sho1, known to regulate the Cek1 pathway in yeasts, was indispensable for C. albicans microcolony formation but regulated the Ras1-cAMP pathway instead, based upon diminished intracellular levels of cAMP and reduced expression of core microcolony genes, including HWP1, PGA10, and ECE1, in C. albicans sho1Δ cells. Based upon predicted physical interactions between Sho1 and the glycolytic enzymes Pfk1, Fba1, Pgk1, and Cdc19, we hypothesized that Sho1 regulates Ras1-cAMP by establishing cellular energy levels produced by glycolysis. Indeed, microcolony formation was restored in C. albicans sho1Δ cells by addition of exogenous intermediates of glycolysis, including downstream products of each predicted interacting enzyme (fructose 1,6 bisphosphate, glyceraldehyde phosphate, 3-phosphoglyceric acid, and pyruvate). Thus, C. albicans Sho1 is an upstream regulator of the Ras1-cAMP signaling pathway that connects glycolytic metabolism to the formation of pathogenic microcolonies. IMPORTANCE C. albicans microcolonies form extensive hyphal structures that enhance surface adherence and penetrate underlying tissues to promote fungal infections. This study examined the environmental conditions that promote microcolony formation and how these signals are relayed, in order to disrupt signaling and reduce pathogenesis. We found that a membrane-localized protein, Sho1, is an upstream regulator of glycolysis and required for Ras1-cAMP signaling. Sho1 controlled the Ras1-dependent expression of core microcolony genes involved in adhesion and virulence. This new regulatory function for Sho1 linking glycolysis to microcolony formation reveals a novel role for this fungal membrane protein.
format	article
author	Rohitashw Kumar Malabika Maulik Ruvini U. Pathirana Paul J. Cullen Mira Edgerton
author_facet	Rohitashw Kumar Malabika Maulik Ruvini U. Pathirana Paul J. Cullen Mira Edgerton
author_sort	Rohitashw Kumar
title	Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
title_short	Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
title_full	Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	sho1p connects glycolysis to ras1-camp signaling and is required for microcolony formation in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/1337f62bf57946ed89116615b43729a5
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Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in <named-content content-type="genus-species">Candida albicans</named-content>

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