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The dimorphic switch from a single-cell budding yeast to a filamentous form enables Saccharomyces cerevisiae to forage for nutrients and the opportunistic pathogen Candida albicans to invade human tissues and evade the immune system. We constructed a genome-wide set of targeted deletion alleles and introduced them into a filamentous S. cerevisiae strain,(More)
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(More)
A common hallmark of many fungal species is the capacity to undergo cellular morphogenesis programs, which, for fungal pathogens, play critical roles in sexual reproduction, nutrient acquisition and virulence. 1 Fungal morphogenesis comprises a diversity of processes, 1,2 ranging from spore germination and branching in filamentous fungi such as the pathogen(More)
BACKGROUND Hsp90 is an environmentally contingent molecular chaperone that influences the form and function of diverse regulators of cellular signaling. Hsp90 potentiates the evolution of fungal drug resistance by enabling crucial cellular stress responses. Here we demonstrate that in the leading fungal pathogen of humans, Candida albicans, Hsp90 governs(More)
The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with -10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in(More)
The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal morphogenesis, biofilm development, drug resistance, and virulence. Hsp90 functions in concert with co-chaperones to regulate stability and activation of client proteins, many of which are signal transducers. Here, we characterize the first Hsp90 co-chaperone in the leading(More)
The trimorphic fungus Candida albicans is the leading cause of systemic candidiasis, a disease with poor prognosis affecting immunocompromised individuals. The capacity of C. albicans to transition between morphological states is a key determinant of its ability to cause life-threatening infection. Recently the molecular chaperone heat shock protein 90(More)
Temperature is a critical and ubiquitous environmental signal that governs the development and virulence of diverse microbial species, including viruses, archaea, bacteria, fungi, and parasites. Microbial survival is contingent upon initiating appropriate responses to the cellular stress induced by severe environmental temperature change. In the case of(More)
The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Introduction Combatting infectious disease is a critical global health concern and involves tackling both emerging infectious agents and newly–drug resistant strains of previously curable pathogens. The widespread and inappropriate(More)
Here we present a generalized method of guide RNA " tuning " that enables Cas9 to discriminate between two target sites that differ by a single nucleotide polymorphism. We employ our methodology to generate a novel in vivo mutation prevention system in which Cas9 actively restricts the occurrence of undesired gain-of-function mutations within a population(More)