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N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans.

Huang G, Yi S, Sahni N, Daniels KJ, Srikantha T, Soll DR - PLoS Pathog. (2010)

Bottom Line: Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans.Recently, however, it was demonstrated that high levels of CO(2), equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox.Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America.

ABSTRACT
To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO(2), equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans.

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A model of the regulatory circuitry involved in the induction of the white to opaque switch.The number of plus signs and the thickness of initial pathway arrows reflect the degree of induction. Note that we have all pathways converging on the master switch gene WOR1 because of their dependency on that gene.
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ppat-1000806-g006: A model of the regulatory circuitry involved in the induction of the white to opaque switch.The number of plus signs and the thickness of initial pathway arrows reflect the degree of induction. Note that we have all pathways converging on the master switch gene WOR1 because of their dependency on that gene.

Mentions: The Ras1/cAMP-dependent pathway has been found to be the predominant one for GlcNAc induction and the minor one for low level CO2 induction [18] (Figure 6). An unidentified pathway has been found to be the predominant one for CO2 induction [18] and an unidentified pathway has the minor one for GlcNAc induction (Figure 6). Our data further suggest that glucose represents a weak but significant inducer of switching that also functions through both a Ras1/cAMP-dependent pathway and a Ras1/cAMP-independent pathway, the latter again unidentified (Figure 6). The fact that each inducer functions not only through the Ras1/cAMP pathway, but also through an unidentified pathway, leaves open the possibility that the Ras1/cAMP-independent pathway may also be common to all three inducers. We demonstrated previously that both the Ras1/cAMP-dependent and -independent pathways for CO2 induction are dependent on Wor1 [18], and we have demonstrated here that the dependent and independent pathways for G1cNAc and glucose induction are also dependent on Wor1. We have demonstrated that only the major portion of G1cNAc induction, which is transduced by the Ras1/cAMP pathway, requires the phosphorylated form of Wor1.


N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans.

Huang G, Yi S, Sahni N, Daniels KJ, Srikantha T, Soll DR - PLoS Pathog. (2010)

A model of the regulatory circuitry involved in the induction of the white to opaque switch.The number of plus signs and the thickness of initial pathway arrows reflect the degree of induction. Note that we have all pathways converging on the master switch gene WOR1 because of their dependency on that gene.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837409&req=5

ppat-1000806-g006: A model of the regulatory circuitry involved in the induction of the white to opaque switch.The number of plus signs and the thickness of initial pathway arrows reflect the degree of induction. Note that we have all pathways converging on the master switch gene WOR1 because of their dependency on that gene.
Mentions: The Ras1/cAMP-dependent pathway has been found to be the predominant one for GlcNAc induction and the minor one for low level CO2 induction [18] (Figure 6). An unidentified pathway has been found to be the predominant one for CO2 induction [18] and an unidentified pathway has the minor one for GlcNAc induction (Figure 6). Our data further suggest that glucose represents a weak but significant inducer of switching that also functions through both a Ras1/cAMP-dependent pathway and a Ras1/cAMP-independent pathway, the latter again unidentified (Figure 6). The fact that each inducer functions not only through the Ras1/cAMP pathway, but also through an unidentified pathway, leaves open the possibility that the Ras1/cAMP-independent pathway may also be common to all three inducers. We demonstrated previously that both the Ras1/cAMP-dependent and -independent pathways for CO2 induction are dependent on Wor1 [18], and we have demonstrated here that the dependent and independent pathways for G1cNAc and glucose induction are also dependent on Wor1. We have demonstrated that only the major portion of G1cNAc induction, which is transduced by the Ras1/cAMP pathway, requires the phosphorylated form of Wor1.

Bottom Line: Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans.Recently, however, it was demonstrated that high levels of CO(2), equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox.Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America.

ABSTRACT
To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO(2), equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans.

Show MeSH
Related in: MedlinePlus