1887

Abstract

The Ras1 signal transduction pathway controls the ability of the pathogenic fungus to grow at high temperatures and to mate. A second gene was identified in this organism. is expressed at a very low level compared to , and a mutation caused no alterations in vegetative growth rate, differentiation or virulence factor expression. The mutant strain was equally virulent to the wild-type strain in the murine inhalational model of cryptococcosis. Although a double mutant strain is viable, mutation of both genes results in a decreased growth rate at all temperatures compared to strains with either single mutation. Overexpression of the gene completely suppressed the mutant mating defect and partially suppressed its high temperature growth defect. After prolonged incubation at a restrictive temperature, the mutant demonstrated actin polarity defects that were also partially suppressed by overexpression. These studies indicate that the Ras1 and Ras2 proteins share overlapping functions, but also play distinct signalling roles. Our findings also suggest a mechanism by which Ras1 controls growth of this pathogenic fungus at 37 °C, supporting a conserved role for Ras homologues in microbial cellular differentiation, morphogenesis and virulence.

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2002-01-01
2020-08-10
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