<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque

ABSTRACT Candida albicans, a pervasive opportunistic pathogen, undergoes a unique phenotypic transition from a “white” phenotype to an “opaque” phenotype. The switch to opaque impacts gene expression, cell morphology, wall structure, metabolism, biofilm formation, mating, virulence, and colonization...

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Autores principales:	Yang-Nim Park, Claude Pujol, Deborah J. Wessels, David R. Soll
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans Candida albicans mating EFG1 WOR1 gray phenotype opaque phenotype switching Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c6f5c95f34384faf8f16920846455add
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spelling	oai:doaj.org-article:c6f5c95f34384faf8f16920846455add2021-11-15T15:30:58Z<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque10.1128/mSphere.00918-202379-5042https://doaj.org/article/c6f5c95f34384faf8f16920846455add2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00918-20https://doaj.org/toc/2379-5042ABSTRACT Candida albicans, a pervasive opportunistic pathogen, undergoes a unique phenotypic transition from a “white” phenotype to an “opaque” phenotype. The switch to opaque impacts gene expression, cell morphology, wall structure, metabolism, biofilm formation, mating, virulence, and colonization of the skin and gastrointestinal (GI) tract. Although the regulation of switching is complex, a paradigm has evolved from a number of studies, in which, in its simplest form, the transcription factors Efg1 and Wor1 play central roles. When EFG1 is upregulated under physiological conditions, it represses WOR1, an activator of white-to-opaque switching, and the cell expresses the white phenotype; when EFG1 is downregulated, WOR1 is derepressed and activates expression of the opaque phenotype. Deletion of either EFG1 or WOR1 supports this yin-yang model of regulation. Here, we demonstrate that this simple model is insufficient, since strains in which WOR1 and EFG1 are simultaneously deleted can still be induced to switch en masse from white to opaque. Opaque cells of double mutants (efg1−/− wor1−/−) are enlarged and elongate, form an enlarged vacuole, upregulate mCherry under the control of an opaque-specific promoter, form opaque cell wall pimples, express the opaque phenotype in lower GI colonization, and, if MTL homozygous, form conjugation tubes in response to pheromone and mate. These results can be explained if the basic and simplified model is expanded to include a WOR1-independent alternative opaque pathway repressed by EFG1. IMPORTANCE The switch from white to opaque in Candida albicans was discovered 33 years ago, but it is still unclear how it is regulated. A regulatory paradigm has emerged in which two transacting factors, Efg1 and Wor1, play central roles, Efg1 as a repressor of WOR1, which encodes an activator of the transition to the opaque phenotype. However, we show here that if both EFG1 and WOR1 are deleted simultaneously, bona fide opaque cells can still be induced en masse. These results are not compatible with the simple paradigm, suggesting that an alternative opaque pathway (AOP) exists, which can activate expression of opaque and, like WOR1, is repressed by EFG1.Yang-Nim ParkClaude PujolDeborah J. WesselsDavid R. SollAmerican Society for MicrobiologyarticleCandida albicansCandida albicans matingEFG1WOR1gray phenotypeopaque phenotype switchingMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Candida albicans mating EFG1 WOR1 gray phenotype opaque phenotype switching Microbiology QR1-502
spellingShingle	Candida albicans Candida albicans mating EFG1 WOR1 gray phenotype opaque phenotype switching Microbiology QR1-502 Yang-Nim Park Claude Pujol Deborah J. Wessels David R. Soll <named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
description	ABSTRACT Candida albicans, a pervasive opportunistic pathogen, undergoes a unique phenotypic transition from a “white” phenotype to an “opaque” phenotype. The switch to opaque impacts gene expression, cell morphology, wall structure, metabolism, biofilm formation, mating, virulence, and colonization of the skin and gastrointestinal (GI) tract. Although the regulation of switching is complex, a paradigm has evolved from a number of studies, in which, in its simplest form, the transcription factors Efg1 and Wor1 play central roles. When EFG1 is upregulated under physiological conditions, it represses WOR1, an activator of white-to-opaque switching, and the cell expresses the white phenotype; when EFG1 is downregulated, WOR1 is derepressed and activates expression of the opaque phenotype. Deletion of either EFG1 or WOR1 supports this yin-yang model of regulation. Here, we demonstrate that this simple model is insufficient, since strains in which WOR1 and EFG1 are simultaneously deleted can still be induced to switch en masse from white to opaque. Opaque cells of double mutants (efg1−/− wor1−/−) are enlarged and elongate, form an enlarged vacuole, upregulate mCherry under the control of an opaque-specific promoter, form opaque cell wall pimples, express the opaque phenotype in lower GI colonization, and, if MTL homozygous, form conjugation tubes in response to pheromone and mate. These results can be explained if the basic and simplified model is expanded to include a WOR1-independent alternative opaque pathway repressed by EFG1. IMPORTANCE The switch from white to opaque in Candida albicans was discovered 33 years ago, but it is still unclear how it is regulated. A regulatory paradigm has emerged in which two transacting factors, Efg1 and Wor1, play central roles, Efg1 as a repressor of WOR1, which encodes an activator of the transition to the opaque phenotype. However, we show here that if both EFG1 and WOR1 are deleted simultaneously, bona fide opaque cells can still be induced en masse. These results are not compatible with the simple paradigm, suggesting that an alternative opaque pathway (AOP) exists, which can activate expression of opaque and, like WOR1, is repressed by EFG1.
format	article
author	Yang-Nim Park Claude Pujol Deborah J. Wessels David R. Soll
author_facet	Yang-Nim Park Claude Pujol Deborah J. Wessels David R. Soll
author_sort	Yang-Nim Park
title	<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
title_short	<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
title_full	<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
title_fullStr	<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
title_full_unstemmed	<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque
title_sort	<named-content content-type="genus-species">candida albicans</named-content> double mutants lacking both <italic toggle="yes">efg1</italic> and <italic toggle="yes">wor1</italic> can still switch to opaque
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c6f5c95f34384faf8f16920846455add
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<named-content content-type="genus-species">Candida albicans</named-content> Double Mutants Lacking both <italic toggle="yes">EFG1</italic> and <italic toggle="yes">WOR1</italic> Can Still Switch to Opaque

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