Pho85, Pcl1, and Hms1 signaling governs Candida albicans morphogenesis induced by high temperature or Hsp90 compromise.
Curr Biol, 2012/3/20;22(6):461-70.
Shapiro RS[1], Sellam A, Tebbji F, Whiteway M, Nantel A, Cowen LE
Affiliations
PMID: 22365851DOI: 10.1016/j.cub.2012.01.062
Impact factor: 10.9
Abstract
background: Temperature exerts powerful control over development and virulence of diverse pathogens. In the leading human fungal pathogen, Candida albicans, temperature governs morphogenesis, a key virulence trait. Many cues that induce the yeast to filament transition are contingent on a minimum of 37°C, whereas further elevation to 39°C serves as an independent inducer. The molecular chaperone Hsp90 is a key regulator of C. albicans temperature-dependent morphogenesis. Compromise of Hsp90 function genetically, pharmacologically, or by elevated temperature induces filamentation in a manner that depends on protein kinase A signaling but is independent of the terminal transcription factor, Efg1.
results: Here, we establish that despite morphological and regulatory differences, inhibition of Hsp90 induces a transcriptional profile similar to that induced by other filamentation cues and does so independently of Efg1. Further, we identify Hms1 as a transcriptional regulator required for morphogenesis induced by elevated temperature or Hsp90 compromise. Hms1 functions downstream of the cyclin Pcl1 and the cyclin-dependent kinase Pho85, both of which are required for temperature-dependent filamentation. Upon Hsp90 inhibition, Hms1 binds to DNA elements involved in filamentous growth, including UME6 and RBT5, and regulates their expression, providing a mechanism through which Pho85, Pcl1, and Hms1 govern morphogenesis. Consistent with the importance of morphogenetic flexibility for virulence, deletion of C. albicans HMS1 attenuates virulence in a metazoan model of infection.
conclusions: Thus, we establish a new mechanism through which Hsp90 orchestrates C. albicans morphogenesis, and define novel regulatory circuitry governing a temperature-dependent developmental program, with broad implications for temperature sensing and virulence of microbial pathogens.
MeSH terms
Animals; Benzoquinones; Candida albicans; Cyclin-Dependent Kinases; Cyclins; Epistasis, Genetic; Fungal Proteins; Genes, Fungal; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Morphogenesis; Moths; Signal Transduction; Temperature; Virulence
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