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MTL-independent phenotypic switching in Candida tropicalis and a dual role for Wor1 in regulating switching and filamentation.

ABSTRACT: Phenotypic switching allows for rapid transitions between alternative cell states and is important in pathogenic fungi for colonization and infection of different host niches. In Candida albicans, the white-opaque phenotypic switch plays a central role in regulating the program of sexual mating as well as interactions with the mammalian host. White-opaque switching is controlled by genes encoded at the MTL (mating-type-like) locus that ensures that only a or ? cells can switch from the white state to the mating-competent opaque state, while a/? cells are refractory to switching. Here, we show that the related pathogen C. tropicalis undergoes white-opaque switching in all three cell types (a, ?, and a/?), and thus switching is independent of MTL control. We also demonstrate that C. tropicalis white cells are themselves mating-competent, albeit at a lower efficiency than opaque cells. Transcriptional profiling of C. tropicalis white and opaque cells reveals significant overlap between switch-regulated genes in MTL homozygous and MTL heterozygous cells, although twice as many genes are white-opaque regulated in a/? cells as in a cells. In C. albicans, the transcription factor Wor1 is the master regulator of the white-opaque switch, and we show that Wor1 also regulates switching in C. tropicalis; deletion of WOR1 locks a, ?, and a/? cells in the white state, while WOR1 overexpression induces these cells to adopt the opaque state. Furthermore, we show that WOR1 overexpression promotes both filamentous growth and biofilm formation in C. tropicalis, independent of the white-opaque switch. These results demonstrate an expanded role for C. tropicalis Wor1, including the regulation of processes necessary for infection of the mammalian host. We discuss these findings in light of the ancestral role of Wor1 as a transcriptional regulator of the transition between yeast form and filamentous growth.

SUBMITTER: Porman AM

PROVIDER: S-EPMC3605238 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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MTL-independent phenotypic switching in Candida tropicalis and a dual role for Wor1 in regulating switching and filamentation.

Porman Allison M AM Hirakawa Matthew P MP Jones Stephen K SK Wang Na N Bennett Richard J RJ

PLoS genetics 20130321 3

Phenotypic switching allows for rapid transitions between alternative cell states and is important in pathogenic fungi for colonization and infection of different host niches. In Candida albicans, the white-opaque phenotypic switch plays a central role in regulating the program of sexual mating as well as interactions with the mammalian host. White-opaque switching is controlled by genes encoded at the MTL (mating-type-like) locus that ensures that only a or α cells can switch from the white sta ...[more]

PMID: 23555286

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Project description:Phenotypic plasticity is a common strategy adopted by fungal pathogens to adapt to diverse host environments. Candida haemulonii is an emerging multidrug-resistant human pathogen that is closely related to Candida auris. Until recently, it was assumed that C. haemulonii is incapable of phenotypic switching or filamentous growth. In this study, we report the identification of three distinct phenotypes in C. haemulonii: white, pink, and filament. The white and pink phenotypes differ in cellular size, colony morphology, and coloration on phloxine B- or CuSO4-containing agar. Switching between the white and pink cell types is heritable and reversible and is referred to as "the primary switching system." The additional switch phenotype, filament, has been identified and exhibits obviously filamentous morphology when grown on glycerol-containing medium. Several unique characteristics of the filamentous phenotype suggest that switching from or to this phenotype poses as a second yeast-filament switching system. The yeast-filament switch is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote filament-yeast transition. We further demonstrated that numerous aspects of the distinct cell types differ in numerous biological aspects, including their high temperature response, specific gene expression, CuSO4 tolerance, secreted aspartyl protease (SAP) activity, and virulence. Therefore, transition among the three phenotypes could enable C. haemulonii to rapidly adapt to, survive, and thrive in certain host niches, thereby contributing to its virulence. IMPORTANCE The capacity to switch between distinct cell types, known as phenotypic switching, is a common strategy adopted by Candida species to adapt to diverse environments. Despite considerable studies on phenotypic plasticity of various Candida species, Candida haemulonii is considered to be incapable of phenotypic switching or filamentous growth. Here, we report and describe filamentation and three distinct phenotypes (white, pink, and filament) in C. haemulonii. The three cell types differ in cellular and colony appearance, gene expression profiles, CuSO4 tolerance, and virulence. C. haemulonii cells switch heritably and reversibly between white and pink cell types, which is referred to as the "primary switching system." Switching between pink and filamentous phenotypes is nonheritable and temperature-dependent, representing a second switching system. As in other Candida species, switching among distinct morphological types may provide C. haemulonii with phenotypic plasticity for rapid responses to the changing host environment, and may contribute to its virulence.

Project description:IntroductionProbiotic Lactobacillus strains had been investigated for the potential to protect against infection caused by the major fungal pathogen of human, Candida albicans. Besides antifungal activity, lactobacilli demonstrated a promising inhibitory effect on biofilm formation and filamentation of C. albicans. On the other hand, two commonly isolated non-albicans Candida species, C. tropicalis and C. parapsilosis, have similar characteristics in filamentation and biofilm formation with C. albicans. However, there is scant information of the effect of lactobacilli on the two species.MethodsIn this study, biofilm inhibitory effects of L. rhamnosus ATCC 53103, L. plantarum ATCC 8014, and L. acidophilus ATCC 4356 were tested on the reference strain C. albicans SC5314 and six bloodstream isolated clinical strains, two each of C. albicans, C. tropicalis, and C. parapsilosis.Results and discussionCell-free culture supernatants (CFSs) of L. rhamnosus and L. plantarum significantly inhibited in vitro biofilm growth of C. albicans and C. tropicalis. L. acidophilus, conversely, had little effect on C. albicans and C. tropicalis but was more effective on inhibiting C. parapsilosis biofilms. Neutralized L. rhamnosus CFS at pH 7 retained the inhibitory effect, suggesting that exometabolites other than lactic acid produced by the Lactobacillus strain might be accounted for the effect. Furthermore, we evaluated the inhibitory effects of L. rhamnosus and L. plantarum CFSs on the filamentation of C. albicans and C. tropicalis strains. Significantly less Candida filaments were observed after co-incubating with CFSs under hyphae-inducing conditions. Expressions of six biofilm-related genes (ALS1, ALS3, BCR1, EFG1, TEC1, and UME6 in C. albicans and corresponding orthologs in C. tropicalis) in biofilms co-incubated with CFSs were analyzed using quantitative real-time PCR. When compared to untreated control, the expressions of ALS1, ALS3, EFG1, and TEC1 genes were downregulated in C. albicans biofilm. In C. tropicalis biofilms, ALS3 and UME6 were downregulated while TEC1 was upregulated. Taken together, the L. rhamnosus and L. plantarum strains demonstrated an inhibitory effect, which is likely mediated by the metabolites secreted into culture medium, on filamentation and biofilm formation of C. albicans and C. tropicalis. Our finding suggested an alternative to antifungals for controlling Candida biofilm.

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MTL-independent phenotypic switching in Candida tropicalis and a dual role for Wor1 in regulating switching and filamentation.

Publications

MTL-independent phenotypic switching in Candida tropicalis and a dual role for Wor1 in regulating switching and filamentation.

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