Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America

Table 1

C. gattii virulence factors and their functions.

Factor	Function
Capsule and its associated polysaccharides	Evasion of phagocytosis [67]
	Reduction of antigen presentation [68]
	Reduction of cytokine production [69]
	Induction of suppressor T-cells which inhibit cell-mediated immunity [70]
	Inhibition of T-cell responses by GXM [31]
	Inhibition of leukocyte migration into inflammatory sites by GXM [31, 71]
Melanin	Protection against UV radiation [72]
	Protection against oxygen and nitrogen free radicals [73, 74]
	May contribute to central nervous system tropism [6]
	Contributes to negative cellular charge [75]
Mannitol	Suggested increase in intracranial pressure [76]
	Protection against stress [77]
	Protection against oxygen free radicals [78]
Extracellular protease	Proteolytic activity [79]
	May contribute to degradation of proteins involved in tissue integrity and host immunity [79–82]
Products of laccase pathway	Diphenol oxidation [83]
	Synthesis of melanin [84]
	Degradation of wood lignin [15]
Superoxide dismutase	Protection against oxidative stress [85]
	Protection against oxidative burst produced by immune effector cells [85]
Phospholipases	Tissue invasion via degradation of mammalian membrane lipids and lung surfactant [15, 86]
Urease	Exact function is unknown [87]
	May aid in transfer of Cryptococcus to central nervous system [88]
STE1𝛼 transcription factor (in cells of 𝛼 mating type)	Upregulation leads to synthesis of diphenol oxidase (which is a laccase) [89, 90]
Growth at physiological temperature (37^∘C)	Survival and persistence in the host [15]
Tolerance of low pH	Survival and persistence in the environment [47]
Tolerance of elevated salt	Survival and persistence in the environment [47]
Phenotypic switching	Change in capsule size—mucoid variant more virulent, smooth variant suggested to be able to cross blood-brain barrier [91]