1. Cryptococcus: Mycology and Virulence
Professor Malcolm D. Richardson
Mycology Reference Centre, Manchester
Manchester University NHS Foundation Trust

2. Intended learning outcomes
To be aware of the common species and habitats of Cryptococcus
To understand the structure of Cryptococcus yeasts
To be aware of the different serotypes of Cryptococcus spp.
To be aware of the virulence factors of Cryptococcus spp.

3. Cryptococcus
Ubiquitous encapsulated yeasts belonging to the division Basidiomycota.
Over 70 species of Cryptococcus are known, however, Cryptococcus neoformans and C. gattii are the two main species implicated in nearly all cases of human cryptococcosis.
C. neoformans has 2 distinct varieties:
C. neoformans var. neoformans
C. neoformans var. grubii
Other species of less clinical significance includes:
C. laurentii, C. adeliensis, C. albidus, etc.

4. Structure Yeast: round or oval Surrounded by polysaccharide capsules
4-6mm in diameter
Surrounded by polysaccharide capsules
20-30mm thick
“Titan” cells ~ mm
Melanised
Negatively stains with India Ink and nigrosin
Stains with PAS and mucicarmine

5. Habitat C. neoformans C. gattii
Frequently isolated from soil contaminated with pigeon or other bird droppings and NOT in fresh wet droppings.
The precise link between C. neoformans and birds to date remains unclear.
Birds do not get infected.
C. gattii
Isolated from decaying wood in the red gum group of eucalyptus trees, cedar, oak and other native trees.
C. gattii has not been isolated from bird droppings.

6. Serotypes of Cryptococcus spp.
PATHOGEN
SEROTYPE
GEOGRAPHICAL
DISTRIBUTION
ENVIRONMENTAL
ASSOCIATION
AFFECTED
PATIENT GROUPS
C. neoformans
var grubii A
Worldwide
Birds, particularly pigeon excreta
HIV patients (98% of all isolates )
Immunocompromised patients
Rarely immunocompetent
C. gattii
B,C
Tropics and subtropics
Eucalyptus trees
Immunocompetent patients
var neoformans D
European countries
var grubii/var neoformans hybrid AD
Not known
Rare clinical isolate
Immunocompromised
JN Day :Practical Neurology, 2004, 4, 274–285

7. Virulence factors Major virulence Other virulence
Polysaccharide capsule formation
Melanin pigment production
Ability to grow well at 370C
Phenotypic switching
Other virulence
Secreted phospholipase B
Urease production
Enzymes associated with protection against oxidative stresses

8. Virulence factors Polysaccharide capsule formation Key roles
Comprised of glucuronoxylomannan (GXM) and galactoxylomannan (GalXM)
Key roles
Anti-phagocytic
Antibody unresponsiveness
Inhibition of leucocyte migration
Deregulation of cytokine secretion
Interference with antigen presentation
L-selectin & tumor necrosis factor loss

9. Virulence factors Melanin pigment production Key Roles Antioxidant
Catalyzed by the enzyme Phenol oxidase
Key Roles
Antioxidant
Cell wall support and integrity
Interference with T-cell response
Reduction of susceptibility to antifungal agents
Abrogation of antibody mediated phagocytosis
Protection from extreme temperature

10. Virulence factors Phenotypic switching Occurs during chronic infection
Common in serotype A and D strains of C. neoformans
Associated with differential gene expression and capsule changes in virulence
“Titan” cell formation
Titan cells
Normal sized cell
Titan cell

11. Summary Cryptococcus are ubiquitous encapsulated yeasts.
C. neoformans and C. gatti are the two main species implicated in clinical disease.
Cryptococcus spp. have a number of virulence factors.
C. neoformans var. grubii (serotype A) is the most common cause of disseminated disease in HIV/AIDs patients.

12. END