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Networks of fibers and factors: regulation of capsule formation in Cryptococcus neoformans.

Ding H, Mayer FL, Sánchez-León E, de S Araújo GR, Frases S, Kronstad JW - F1000Res (2016)

Bottom Line: The ability of the pathogenic fungus Cryptococcus neoformans to cause life-threatening meningoencephalitis in immunocompromised individuals is due in large part to elaboration of a capsule consisting of polysaccharide fibers.Recent studies reveal a complex network of transcription factors that influence capsule elaboration in response to several different signals of relevance to disease (e.g., iron deprivation).The emerging complexity of the network is consistent with the diversity of conditions that influence the capsule and illustrates the responsiveness of the fungus to both the environment and mammalian hosts.

View Article: PubMed Central - PubMed

Affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.

ABSTRACT
The ability of the pathogenic fungus Cryptococcus neoformans to cause life-threatening meningoencephalitis in immunocompromised individuals is due in large part to elaboration of a capsule consisting of polysaccharide fibers. The size of the cell-associated capsule is remarkably responsive to a variety of environmental and host conditions, but the mechanistic details of the regulation, synthesis, trafficking, and attachment of the polysaccharides are poorly understood. Recent studies reveal a complex network of transcription factors that influence capsule elaboration in response to several different signals of relevance to disease (e.g., iron deprivation). The emerging complexity of the network is consistent with the diversity of conditions that influence the capsule and illustrates the responsiveness of the fungus to both the environment and mammalian hosts.

No MeSH data available.


Related in: MedlinePlus

A network of transcription factors affecting capsule size inCryptococcus neoformans.The connections between transcription factors and the information on capsule sizes for the corresponding mutants were adapted from Maieret al.30, Gishet al.32, Junget al.25, and CryptoNet (www.inetbio.org/cryptonet)27. The colors of the transcription factors indicate the different groups, and the white factors do not clearly fit in any of the four groups. Small up and down arrows indicate upregulation and downregulation of functions in the different groups, respectively. *Capsule size may differ between specific studies owing to differences in growth conditions. **These mutants have hypervariable capsule sizes. Abbreviations: AA, amino acid; ROS, reactive oxygen species, WT, wild-type.
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f2: A network of transcription factors affecting capsule size inCryptococcus neoformans.The connections between transcription factors and the information on capsule sizes for the corresponding mutants were adapted from Maieret al.30, Gishet al.32, Junget al.25, and CryptoNet (www.inetbio.org/cryptonet)27. The colors of the transcription factors indicate the different groups, and the white factors do not clearly fit in any of the four groups. Small up and down arrows indicate upregulation and downregulation of functions in the different groups, respectively. *Capsule size may differ between specific studies owing to differences in growth conditions. **These mutants have hypervariable capsule sizes. Abbreviations: AA, amino acid; ROS, reactive oxygen species, WT, wild-type.

Mentions: Maieret al.30 also examined the transcriptional dynamics of capsule induction by RNA-seq on wild-type cells upon transfer from rich media to capsule-inducing conditions and discovered that genes involved in protein translation were down-regulated, whereas genes with functions in specific amino acid synthesis and protein degradation were induced, consistent with other studies28,29. Moreover, based on temporal expression patterns of TFs during capsule induction, Maieret al.30 were able to build a hierarchical network of four groups of TFs and regulatory proteins such as signaling components. Group 1 TFs sit on top of the hierarchy, with expression levels slightly increased within 90 minutes of transfer and sharply decreased over the next 24 hours. These TFs include activators of ribosome biogenesis, repressors of mitochondria-encoded respiration genes, and repressors of a cluster of capsule-involved genes. Group 2 TFs are repressed by TFs of Group 1, hence having expression profiles opposite to the factors in Group 1. These TFs regulate mitochondria-encoded respiration genes and genes involved in capsule formation that do not encode TFs. Group 3 regulators have similar expression profiles to Group 2 with decreased expression within the first 90 minutes followed by increased transcript levels, except that the expression levels never recovered to initial abundance. Group 3 regulators appear to activate genes in response to reactive oxygen species and to repress genes encoding carbohydrate and amino acid transporters. Group 4 regulators do not regulate the genes in other groups and therefore sit at the bottom of the hierarchy. The expression of these genes steadily increased within 24 hours upon transferring from rich media to capsule-inducing conditions.Figure 2 presents a schematic of the network defined by the four groups identified by Maieret al.30, with representative genes within each group and additional TFs and regulatory proteins from other studies18,25,27,32. It is noteworthy that each study employed specific capsule-inducing approaches and the structure of the network may therefore be condition dependent. Nevertheless, the approach in combination with PhenoProphet and temporal expression pattern analysis provides a powerful tool for building regulatory networks.


Networks of fibers and factors: regulation of capsule formation in Cryptococcus neoformans.

Ding H, Mayer FL, Sánchez-León E, de S Araújo GR, Frases S, Kronstad JW - F1000Res (2016)

A network of transcription factors affecting capsule size inCryptococcus neoformans.The connections between transcription factors and the information on capsule sizes for the corresponding mutants were adapted from Maieret al.30, Gishet al.32, Junget al.25, and CryptoNet (www.inetbio.org/cryptonet)27. The colors of the transcription factors indicate the different groups, and the white factors do not clearly fit in any of the four groups. Small up and down arrows indicate upregulation and downregulation of functions in the different groups, respectively. *Capsule size may differ between specific studies owing to differences in growth conditions. **These mutants have hypervariable capsule sizes. Abbreviations: AA, amino acid; ROS, reactive oxygen species, WT, wild-type.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979528&req=5

f2: A network of transcription factors affecting capsule size inCryptococcus neoformans.The connections between transcription factors and the information on capsule sizes for the corresponding mutants were adapted from Maieret al.30, Gishet al.32, Junget al.25, and CryptoNet (www.inetbio.org/cryptonet)27. The colors of the transcription factors indicate the different groups, and the white factors do not clearly fit in any of the four groups. Small up and down arrows indicate upregulation and downregulation of functions in the different groups, respectively. *Capsule size may differ between specific studies owing to differences in growth conditions. **These mutants have hypervariable capsule sizes. Abbreviations: AA, amino acid; ROS, reactive oxygen species, WT, wild-type.
Mentions: Maieret al.30 also examined the transcriptional dynamics of capsule induction by RNA-seq on wild-type cells upon transfer from rich media to capsule-inducing conditions and discovered that genes involved in protein translation were down-regulated, whereas genes with functions in specific amino acid synthesis and protein degradation were induced, consistent with other studies28,29. Moreover, based on temporal expression patterns of TFs during capsule induction, Maieret al.30 were able to build a hierarchical network of four groups of TFs and regulatory proteins such as signaling components. Group 1 TFs sit on top of the hierarchy, with expression levels slightly increased within 90 minutes of transfer and sharply decreased over the next 24 hours. These TFs include activators of ribosome biogenesis, repressors of mitochondria-encoded respiration genes, and repressors of a cluster of capsule-involved genes. Group 2 TFs are repressed by TFs of Group 1, hence having expression profiles opposite to the factors in Group 1. These TFs regulate mitochondria-encoded respiration genes and genes involved in capsule formation that do not encode TFs. Group 3 regulators have similar expression profiles to Group 2 with decreased expression within the first 90 minutes followed by increased transcript levels, except that the expression levels never recovered to initial abundance. Group 3 regulators appear to activate genes in response to reactive oxygen species and to repress genes encoding carbohydrate and amino acid transporters. Group 4 regulators do not regulate the genes in other groups and therefore sit at the bottom of the hierarchy. The expression of these genes steadily increased within 24 hours upon transferring from rich media to capsule-inducing conditions.Figure 2 presents a schematic of the network defined by the four groups identified by Maieret al.30, with representative genes within each group and additional TFs and regulatory proteins from other studies18,25,27,32. It is noteworthy that each study employed specific capsule-inducing approaches and the structure of the network may therefore be condition dependent. Nevertheless, the approach in combination with PhenoProphet and temporal expression pattern analysis provides a powerful tool for building regulatory networks.

Bottom Line: The ability of the pathogenic fungus Cryptococcus neoformans to cause life-threatening meningoencephalitis in immunocompromised individuals is due in large part to elaboration of a capsule consisting of polysaccharide fibers.Recent studies reveal a complex network of transcription factors that influence capsule elaboration in response to several different signals of relevance to disease (e.g., iron deprivation).The emerging complexity of the network is consistent with the diversity of conditions that influence the capsule and illustrates the responsiveness of the fungus to both the environment and mammalian hosts.

View Article: PubMed Central - PubMed

Affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.

ABSTRACT
The ability of the pathogenic fungus Cryptococcus neoformans to cause life-threatening meningoencephalitis in immunocompromised individuals is due in large part to elaboration of a capsule consisting of polysaccharide fibers. The size of the cell-associated capsule is remarkably responsive to a variety of environmental and host conditions, but the mechanistic details of the regulation, synthesis, trafficking, and attachment of the polysaccharides are poorly understood. Recent studies reveal a complex network of transcription factors that influence capsule elaboration in response to several different signals of relevance to disease (e.g., iron deprivation). The emerging complexity of the network is consistent with the diversity of conditions that influence the capsule and illustrates the responsiveness of the fungus to both the environment and mammalian hosts.

No MeSH data available.


Related in: MedlinePlus