TABLE 3

Comparison of cellular functions and virulence of Cryptococcus gattii and Cryptococcus neoformans by using deletion mutants a

Gene(s) of interest, productFunctionPhenotypeRequired for virulence, modelReference(s)
SOD1, superoxide dismutaseCytoplasmic antioxidantRequired for production of virulence factors urease, PLB, and laccase in C. gattii but not C. neoformans Yes, in BALB/c mouse intravenous inoculation model and in A/JCr mouse inhalational model of C. neoformans 390
SOD2, superoxide dismutaseMitochondrial antioxidantRequired for growth at 37°C in 20% but not in 1.3% oxygenYes, for C. gattii BALB/c mouse inhalation and i.v. inoculation model; C. neoformans was not tested 391
TPS1 and TPS2, trehalose-6-phosphate synthaseTrehalose biosynthesis; trehalose functions as an antioxidant and stress protectantRequired for thermotolerance, capsule and melanin production, mating, and cell wall integrity in C. gattii and thermotolerance in C. neoformans Yes, for C. gattii Caenorhabditis elegans (worm) and A/JCr mouse inhalational models; TSP1 but not TSP2 is required for virulence in C. neoformans 392, 393
PKA1, cAMP-activated protein kinase ASignal transduction pathway regulatorRequired for capsule production in C. gattii and mating and capsule and melanin production in C. neoformans C. gattii was not tested; yes, for virulence of C. neoformans in BALB/c mouse inhalational model and immunosuppressed rabbit CSF inoculation model 394, 395
PKA2, cAMP-activated protein kinase ASignal transduction pathway regulatorRequired for mating and capsule and melanin production in C. gattii but not C. neoformans Not tested 394, 395
PLC1 Signal transduction pathway regulatorRegulates growth at 37°C and melanin and PLB production in C. neoformans through the PKC/MAPK pathway (see below)Yes, in C. neoformans BALB/c mouse inhalational model 396
MPK1 Signal transduction pathway regulatorRegulates melanin, capsule production, and cell wall integrity in C. gattii and thermotolerance and cell wall integrity at 37°C in C. neoformans Yes, in C. gattii (BALB/c inhalational model) and in C. neoformans i.v. DBA/2 complement-deficient mouse model 397
STE12αTranscription factorRegulates melanin, mating, and ecological fitness in C. gattii and mating and capsule size in C. neoformans Yes, in C. gattii but not C. neoformans 398, 399
GAT1 GATA transcription factorRegulates nitrogen utilizationYes, in C. gattii but not in C. neoformans BALB/c intrapharyngeal instillation model 400
CNA1, calcineurin catalytic subunit (A)Subunit of the heterodimer calcineurin, a Ca2+ calmodulin-activated serine-threonine-specific protein phosphataseIn C. gattii, regulates thermotolerance (37°C) (strains differ) and is required for plasma membrane integrity, tolerance to fluconazole, and optimal growth in the presence of Ca2+ Li+, with no role in melanin and a minor role in capsule production; in C. neoformans, lesser effect of Ca2+ and not required for fluconazole tolerance inYes, in C. gattii (molecular type-dependent) G. mellonella (wax moth) larva and A/JCr mouse inhalational models and also in C. neoformans rabbit intracisternal inoculation and BALB/c mouse i.v. inoculation models 156, 401, 402
  • a Note the functional divergence between C. gattii and C. neoformans for all genes analyzed, with an evolutionary switch of functions of PKA1 and -2. cAMP, cyclic AMP; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; PLB, phospholipase B.