Journal article
Genetic analysis of the Candida albicans biofilm transcription factor network using simple and complex haploinsufficiency
PLoS genetics, Vol.13(8), pp.e1006948-e1006948
08/2017
DOI: 10.1371/journal.pgen.1006948
PMCID: PMC5565191
PMID: 28793308
Abstract
Biofilm formation by Candida albicans is a key aspect of its pathobiology and is regulated by an integrated network of transcription factors (Bcr1, Brg1, Efg1, Ndt80, Rob1, and Tec1). To understand the details of how the transcription factors function together to regulate biofilm formation, we used a systematic genetic interaction approach based on generating all possible double heterozygous mutants of the network genes and quantitatively analyzing the genetic interactions between them. Overall, the network is highly susceptible to genetic perturbation with the six network heterozygous mutants all showing alterations in biofilm formation (haploinsufficiency). In addition, many double heterozygous mutants are as severely affected as homozygous deletions. As a result, the network shows properties of a highly interdependent 'small-world' network that is highly efficient but not robust. In addition, these genetic interaction data indicate that TEC1 represents a network component whose expression is highly sensitive to small perturbations in the function of other networks TFs. We have also found that expression of ROB1 is dependent on both auto-regulation and cooperative interactions with other network TFs. Finally, the heterozygous NDT80 deletion mutant is hyperfilamentous under both biofilm and hyphae-inducing conditions in a TEC1-dependent manner. Taken together, genetic interaction analysis of this network has provided new insights into the functions of individual TFs as well as into the role of the overall network topology in its function.
Details
- Title: Subtitle
- Genetic analysis of the Candida albicans biofilm transcription factor network using simple and complex haploinsufficiency
- Creators
- Virginia E Glazier - Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, United States of AmericaThomas Murante - Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, United States of AmericaDaniel Murante - Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, United States of AmericaKristy Koselny - Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, United States of AmericaYuan Liu - Biofilm Research Laboratory, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of AmericaDongyeop Kim - Biofilm Research Laboratory, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of AmericaHyun Koo - Biofilm Research Laboratory, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of AmericaDamian J Krysan - Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.13(8), pp.e1006948-e1006948
- DOI
- 10.1371/journal.pgen.1006948
- PMID
- 28793308
- PMCID
- PMC5565191
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Publisher
- Public Library Science
- Grant note
- R01 DE025220 / NIDCR NIH HHS R01 AI098450 / NIAID NIH HHS
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093350602771
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