Juan Colazo
Last active: 11/28/2019

Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

Veri AO, Miao Z, Shapiro RS, Tebbji F, O'Meara TR, Kim SH, Colazo J, Tan K, Vyas VK, Whiteway M, Robbins N, Wong KH, Cowen LE
PLoS Genet. 2018 14 (3): e1007270

PMID: 29590106 · PMCID: PMC5873724 · DOI:10.1371/journal.pgen.1007270

The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.

MeSH Terms (12)

Blotting, Western Candida albicans Chromatin Immunoprecipitation Genes, Fungal Heat Shock Transcription Factors HSP90 Heat-Shock Proteins Morphogenesis Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, RNA Temperature Virulence

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