Cryptococcus: Mycology and - PowerPoint Presentation

Slide1

Cryptococcus: Mycology and Virulence

Professor Malcolm D. Richardson

Mycology Reference

C

entre, Manchester

Manchester University NHS Foundation Trust

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.

Cryptococcus

Ubiquitous encapsulated yeasts belonging to the division Basidiomycota.

Over

7

0

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.

Structure

Yeast: round or oval4-6mm in diameterSurrounded by polysaccharide capsules20-30mm thick “Titan” cells ~90-100 mmMelanised Negatively stains with India Ink and nigrosinStains with PAS and mucicarmine

Habitat

C.

n

eoformans

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.

Serotypes of Cryptococcus spp.

PATHOGENSEROTYPEGEOGRAPHICALDISTRIBUTIONENVIRONMENTAL ASSOCIATIONAFFECTED PATIENT GROUPSC. neoformansvar grubiiAWorldwideBirds, particularly pigeon excretaHIV patients (98% of all isolates )Immunocompromised patients Rarely immunocompetent C. gattiiB,CTropics and subtropicsEucalyptus treesImmunocompetent patients C. neoformansvar neoformansDEuropean countriesBirds, particularly pigeon excretaImmunocompromised patients Rarely immunocompetent C. neoformansvar grubii/var neoformans hybridADNot knownNot known Rare clinical isolateImmunocompromised

JN

Day

:

Practical

Neurology

, 2004, 4, 274–285

Virulence factors

Major virulence Polysaccharide capsule formationMelanin pigment production Ability to grow well at 370CPhenotypic switching

Other virulence

Secreted phospholipase B

Urease production

Enzymes associated with protection against oxidative stresses

Virulence factors

Polysaccharide capsule formationComprised of glucuronoxylomannan (GXM) and galactoxylomannan (GalXM)Key roles Anti-phagocyticAntibody unresponsivenessInhibition of leucocyte migrationDeregulation of cytokine secretionInterference with antigen presentationL-selectin & tumor necrosis factor loss

Virulence factors

Melanin pigment production Catalyzed by the enzyme Phenol oxidase Key Roles AntioxidantCell wall support and integrityInterference with T-cell responseReduction of susceptibility to antifungal agentsAbrogation of antibody mediated phagocytosisProtection from extreme temperature

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

Normal sized cell

Titan cells

Titan cell

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.

END