GPA1 regulates capsule formation, melanin production, mating, and virulence in Cryptococcus neoformans
Virulence of the pathogenic fungus Cryptococcus neoformans is determined by several factors, including the production of a polysaccharide capsule, the elaboration of melanin within the cell wall, and growth at 37°. A gene encoding a cryptococcal G-protein α-subunit, GPA1, was recently identified and found to be induced by nitrogen limitation. To further characterize the biological functions of this gene, we isolated cryptococcal mutant strains in which the GPA1 gene was inactivated by homologous recombination. The gpa1 mutants cells fail to induce capsule in response to CO2 or low iron, and have decreased melanin production and attenuated mating; these three mutant phenotypes were complemented by reintroduction of the wild type GPA1 gene. In a rabbit model of cryptococcal meningitis, the gpa1 mutant strain was considerably less pathogenic compared to the isogenic GPA1 wild type. We conclude that the GPA1 Gα protein is required for pathogenicity, possibly to signal environmental signals to induce the production of virulence factors.
Alspaugh, JA; Perfect, JR; Heitman, J
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