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Circuit diversification in a biofilm regulatory network
Manning Y Huang1, Carol A Woolford1, Gemma May1
1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.
Plos Pathogens
|May 23, 2019
Summary
Circuit diversification, the alteration of gene regulatory relationships, is widespread in Candida albicans. This variation in gene networks explains differences in how fungal pathogens cause infection.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Genotype-phenotype relationships vary within species due to alterations in gene regulatory networks, known as circuit diversification.
- Circuit diversification is a potential driver of speciation through genetic divergence and rewiring.
- The fungal pathogen Candida albicans, a significant cause of infection, forms biofilms with hyphal cells, and its regulatory network is key to understanding this process.
Purpose of the Study:
- To investigate the prevalence of circuit diversification in the biofilm/hyphal regulatory network of Candida albicans.
- To determine how genetic variations in key transcription factors affect biofilm formation across different clinical isolates.
- To elucidate the role of specific gene regulatory relationships in driving genotype-phenotype variations.
Main Methods:
- CRISPR-based gene editing was employed to create mutations in four critical biofilm transcription factor genes (BCR1, UME6, BRG1, EFG1).
- Mutations were introduced into the reference strain SC5314 and four additional clinical isolates of Candida albicans.
- Phenotypic analyses, gene expression profiling (Nanostring and RNA-Seq), and engineered gene expression were used to assess the impact of genetic modifications.
Main Results:
- Mutations in BCR1 and UME6 showed variable effects on phenotypes across different isolates, indicating strain-specific regulatory roles.
- Mutations in BRG1 and EFG1 resulted in consistently severe phenotypic impacts across all tested isolates.
- Gene expression data revealed significant variability in regulatory relationships among the isolates, particularly concerning the control of BRG1 by BCR1.
Conclusions:
- Circuit diversification is a common phenomenon in the Candida albicans biofilm/hyphal regulatory network, not an exception.
- Variations in genotype-phenotype relationships are partly explained by differences in the BCR1 control of BRG1.
- The study highlights the extensive plasticity of gene regulatory networks in microbial pathogens and its implications for infection and evolution.
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