Cell Biology

Warming Up to Its Host

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Science  22 May 2009:
Vol. 324, Issue 5930, pp. 989
DOI: 10.1126/science.324_989c

The fungal pathogen Candida albicans responds to increases in temperature by initiating a transition from growing as a single-celled yeast to a multicellular filamentous form, the latter associated with greater virulence. Shapiro et al. report that inhibition of heat shock protein 90 (Hsp90) was necessary to promote filamentous growth in response to environmental conditions and was sufficient to promote filamentous growth in cells that would normally grow as the budding yeast form. Filament formation in cells with reduced expression of Hsp90 was more sensitive to increased temperature, and lower doses of a pharmacological inhibitor were required to promote filamentous growth at 37°C than at 30°C. Cells with mutations in the Ras1-PKA pathway [from the GTPase Ras1 to the cAMP-dependent protein kinase A (PKA)] failed to respond to inhibition of Hsp90. Genetic experiments also supported a role of Hsp90 in restraining filamentous differentiation by repressing signaling through the Ras1-PKA pathway, and in a mouse model, genetic depletion of Hsp90 completely cleared the kidney of C. albicans.

Curr. Biol. 19, 621 (2009).

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