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Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.

Lin X, Huang JC, Mitchell TG, Heitman J - PLoS Genet. (2006)

Bottom Line: We discovered that variation in hyphal length produced during fruiting is a quantitative trait resulting from the combined effects of multiple genetic loci, including the mating type (MAT) locus.Importantly, the alpha allele of the MAT locus enhanced hyphal growth compared with the a allele.MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

ABSTRACT
Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and monokaryotic fruiting. The traditional sexual cycle that leads to the production of infectious basidiospores involves cells of both alpha and a mating type. Monokaryotic fruiting is a modified form of sexual reproduction that involves cells of the same mating type, most commonly alpha, which is the predominant mating type in both the environment and clinical isolates. However, some a isolates can also undergo monokaryotic fruiting. To determine whether mating type and other genetic loci contribute to the differences in fruiting observed between alpha and a cells, we applied quantitative trait loci (QTL) mapping to an inbred population of F2 progeny. We discovered that variation in hyphal length produced during fruiting is a quantitative trait resulting from the combined effects of multiple genetic loci, including the mating type (MAT) locus. Importantly, the alpha allele of the MAT locus enhanced hyphal growth compared with the a allele. Other virulence traits, including melanization and growth at 39 degrees C, also are quantitative traits that share a common QTL with hyphal growth. The Mac1 transcription factor, encoded in this common QTL, regulates copper homeostasis. MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth. Further characterization of these QTL regions will reveal additional quantitative trait genes controlling biological processes central to fungal development and pathogenicity.

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Mac1 Is a QTG Regulating Growth, Melanization, and Filamentation of C. neoformansWild-type strain XL304α and its mac1 mutant were cultured on YPD medium with the indicated concentrations of BCS or copper sulfate at 22 °C (A) and 39 °C (B). The mac1 mutant showed hypersensitivity under copper-limiting and copper-rich conditions at both temperatures. Wild-type and the mac1 mutant were cultured on L-DOPA medium with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of melanin production (C). The melanin production in mac1 mutant is also hypersensitive to copper in the medium, showing a bell-shaped response similar to growth (C). Wild-type and the mac1 mutant were cultured on V8 medium (pH 7.0) with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of filamentation (D). Filamentation of the mac1 mutant is highly sensitive to copper ions in the medium (D). MAC1 allele exchange indicates different functions of the two alleles (E). Wild-type XL304α, wild-type JEC21α, JEC21α mac1 mutant, and transgenic JEC21α mac1 mutant with the MAC1 XL304α allele were cultured on L-DOPA medium at 22 °C with the indicated concentrations of BCS or copper sulfate (E).
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pgen-0020187-g012: Mac1 Is a QTG Regulating Growth, Melanization, and Filamentation of C. neoformansWild-type strain XL304α and its mac1 mutant were cultured on YPD medium with the indicated concentrations of BCS or copper sulfate at 22 °C (A) and 39 °C (B). The mac1 mutant showed hypersensitivity under copper-limiting and copper-rich conditions at both temperatures. Wild-type and the mac1 mutant were cultured on L-DOPA medium with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of melanin production (C). The melanin production in mac1 mutant is also hypersensitive to copper in the medium, showing a bell-shaped response similar to growth (C). Wild-type and the mac1 mutant were cultured on V8 medium (pH 7.0) with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of filamentation (D). Filamentation of the mac1 mutant is highly sensitive to copper ions in the medium (D). MAC1 allele exchange indicates different functions of the two alleles (E). Wild-type XL304α, wild-type JEC21α, JEC21α mac1 mutant, and transgenic JEC21α mac1 mutant with the MAC1 XL304α allele were cultured on L-DOPA medium at 22 °C with the indicated concentrations of BCS or copper sulfate (E).

Mentions: Deletion of the MAC1 gene in strain XL304α caused growth hypersensitivity of the mutant under both copper-limiting and copper-rich conditions at 22 °C and 39 °C (Figure 12A and 12B). Thus, Mac1 in C. neoformans appears to maintain copper homeostasis under conditions of copper deficiency or repletion. This effect contrasts with that of S. cerevisiae, in which Mac1 is only active at low concentrations of copper [57]. In addition to yeast growth, melanin production and filamentation of the mac1 mutant were also hypersensitive to both copper-limiting and copper-enriched conditions, exhibiting a bell-shaped response (Figure 12C and 12D).


Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.

Lin X, Huang JC, Mitchell TG, Heitman J - PLoS Genet. (2006)

Mac1 Is a QTG Regulating Growth, Melanization, and Filamentation of C. neoformansWild-type strain XL304α and its mac1 mutant were cultured on YPD medium with the indicated concentrations of BCS or copper sulfate at 22 °C (A) and 39 °C (B). The mac1 mutant showed hypersensitivity under copper-limiting and copper-rich conditions at both temperatures. Wild-type and the mac1 mutant were cultured on L-DOPA medium with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of melanin production (C). The melanin production in mac1 mutant is also hypersensitive to copper in the medium, showing a bell-shaped response similar to growth (C). Wild-type and the mac1 mutant were cultured on V8 medium (pH 7.0) with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of filamentation (D). Filamentation of the mac1 mutant is highly sensitive to copper ions in the medium (D). MAC1 allele exchange indicates different functions of the two alleles (E). Wild-type XL304α, wild-type JEC21α, JEC21α mac1 mutant, and transgenic JEC21α mac1 mutant with the MAC1 XL304α allele were cultured on L-DOPA medium at 22 °C with the indicated concentrations of BCS or copper sulfate (E).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC1636697&req=5

pgen-0020187-g012: Mac1 Is a QTG Regulating Growth, Melanization, and Filamentation of C. neoformansWild-type strain XL304α and its mac1 mutant were cultured on YPD medium with the indicated concentrations of BCS or copper sulfate at 22 °C (A) and 39 °C (B). The mac1 mutant showed hypersensitivity under copper-limiting and copper-rich conditions at both temperatures. Wild-type and the mac1 mutant were cultured on L-DOPA medium with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of melanin production (C). The melanin production in mac1 mutant is also hypersensitive to copper in the medium, showing a bell-shaped response similar to growth (C). Wild-type and the mac1 mutant were cultured on V8 medium (pH 7.0) with the indicated concentrations of BCS or copper sulfate at 22 °C for induction of filamentation (D). Filamentation of the mac1 mutant is highly sensitive to copper ions in the medium (D). MAC1 allele exchange indicates different functions of the two alleles (E). Wild-type XL304α, wild-type JEC21α, JEC21α mac1 mutant, and transgenic JEC21α mac1 mutant with the MAC1 XL304α allele were cultured on L-DOPA medium at 22 °C with the indicated concentrations of BCS or copper sulfate (E).
Mentions: Deletion of the MAC1 gene in strain XL304α caused growth hypersensitivity of the mutant under both copper-limiting and copper-rich conditions at 22 °C and 39 °C (Figure 12A and 12B). Thus, Mac1 in C. neoformans appears to maintain copper homeostasis under conditions of copper deficiency or repletion. This effect contrasts with that of S. cerevisiae, in which Mac1 is only active at low concentrations of copper [57]. In addition to yeast growth, melanin production and filamentation of the mac1 mutant were also hypersensitive to both copper-limiting and copper-enriched conditions, exhibiting a bell-shaped response (Figure 12C and 12D).

Bottom Line: We discovered that variation in hyphal length produced during fruiting is a quantitative trait resulting from the combined effects of multiple genetic loci, including the mating type (MAT) locus.Importantly, the alpha allele of the MAT locus enhanced hyphal growth compared with the a allele.MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

ABSTRACT
Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and monokaryotic fruiting. The traditional sexual cycle that leads to the production of infectious basidiospores involves cells of both alpha and a mating type. Monokaryotic fruiting is a modified form of sexual reproduction that involves cells of the same mating type, most commonly alpha, which is the predominant mating type in both the environment and clinical isolates. However, some a isolates can also undergo monokaryotic fruiting. To determine whether mating type and other genetic loci contribute to the differences in fruiting observed between alpha and a cells, we applied quantitative trait loci (QTL) mapping to an inbred population of F2 progeny. We discovered that variation in hyphal length produced during fruiting is a quantitative trait resulting from the combined effects of multiple genetic loci, including the mating type (MAT) locus. Importantly, the alpha allele of the MAT locus enhanced hyphal growth compared with the a allele. Other virulence traits, including melanization and growth at 39 degrees C, also are quantitative traits that share a common QTL with hyphal growth. The Mac1 transcription factor, encoded in this common QTL, regulates copper homeostasis. MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth. Further characterization of these QTL regions will reveal additional quantitative trait genes controlling biological processes central to fungal development and pathogenicity.

Show MeSH
Related in: MedlinePlus