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. Author summary For human pathogens, the capacity to respond to elevated temperature is required for survival, with elevated temperature in the form of fever as a conserved host response to defend against infection. One of the leading fungal pathogens of humans in Candida albicans , which is capable of growing in both a yeast and filamentous state. The ability to transition between these forms is a key virulence trait, and one that is highly temperature-dependent. A pivotal regulator of filamentous growth is the temperature-responsive molecular chaperone Hsp90, which has complex relationships with the transcription factor Hsf1. Although Hsf1 regulates changes in gene expression in response to heat shock, its impact on morphogenesis remains unknown. Here, we uncover an intriguing phenomenon whereby overexpression or depletion of C . albicans HSF1 induces morphogenesis. We observe that HSF1 depletion compromises Hsp90 function, thereby driving filamentation. In contrast, HSF1 overexpression induces a dose-dependent expansion of its transcriptional targets that drives overexpression of positive regulators of filamentous growth. This work illuminates novel mechanisms through which tuning the levels of an environmentally contingent transcription factor drives a key developmental program.
【초록키워드】 Gene Expression, Human, Infection, host response, survival, pathogen, Fever, Control, target, microorganisms, Pathogens, temperature, Hsp90, molecular, virulence, Critical, mechanism, yeast, fungal, cellular, microorganism, Candida albicans, regulate, Heat shock, transcription factor, Regulation, growth, complex, physiological temperature, hosts, Depletion, overexpression, positive, elevated temperature, environmental cues, Hsf1, morphogenesis, chaperone, driving, mammalian, Host, fluctuation, highlight, transcriptional, observé, conserved, required, form, functional, provide, changes in, absence, modulate, induce, dose-dependent, respond, developmental, fungal pathogen, Candida albican, bypassing, defend, environmental cue, 【제목키워드】 fungal, tuning, impairing,