title: The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression.
abstract: BACKGROUND
  The fungal pathogen Candida albicans colonizes the gastrointestinal (GI) tract of mammalian hosts as a benign commensal. However, in an immunocompromised host, the fungus is capable of causing life-threatening infection. We previously showed that the major transcription factor Efg1p is differentially expressed in GI-colonizing C. albicans cells dependent on the host immune status. To understand the mechanisms that underlie this host-dependent differential gene expression, we utilized mathematical modeling to dissect host-pathogen interactions. Specifically, we used principles of evolutionary game theory to study the mechanism that governs dynamics of EFG1 expression during C. albicans colonization.
  
  
  RESULTS
  Mathematical modeling predicted that down-regulation of EFG1 expression within individual fungal cells occurred at different average rates in different hosts. Rather than using relatively transient signaling pathways to adapt to a new environment, we demonstrate that C. albicans overcomes the host defense strategy by modulating the activity of diverse fungal histone modifying enzymes that control EFG1 expression.
  
  
  CONCLUSIONS
  Based on our modeling and experimental results we conclude that C. albicans cells sense the local environment of the GI tract and respond to differences by altering EFG1 expression to establish optimal survival strategies. We show that the overall process is governed via modulation of epigenetic regulators of chromatin structure.
authors.affiliation: Theoretische Biophysik, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115, Berlin, Germany. katarzyna.tyc@gmail.com.|Present address: Department of Biochemistry, University of Utah, Salt Lake City, UT, 84112, USA. katarzyna.tyc@gmail.com.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Tyc
authors.affiliation: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences and Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, 02111, USA. Sanna.Herwald@tufts.edu.
authors.forename: Sanna E
authors.initials: SE
authors.lastname: Herwald
authors.affiliation: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences and Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, 02111, USA. hoganja@gmail.com.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hogan
authors.affiliation: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences and Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, 02111, USA. jvpierce519@gmail.com.|Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. jvpierce519@gmail.com.
authors.forename: Jessica V
authors.initials: JV
authors.lastname: Pierce
authors.affiliation: Theoretische Biophysik, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115, Berlin, Germany. edda.klipp@rz.hu-berlin.de.
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
authors.affiliation: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences and Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, 02111, USA. carol.kumamoto@tufts.edu.|Department of Molecular Biology and Microbiology, Tufts University, 136 Harrison Ave., Boston, MA, 02111, USA. carol.kumamoto@tufts.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kumamoto
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005716:Game Theory; D041981:Gastrointestinal Tract / Q000382:microbiology; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D008954:Models, Biological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014385:Tuberculosis, Gastrointestinal
chemical_list: D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D006657:Histones; D014157:Transcription Factors