Yeast

This section will explore the major players like Candida, Cryptococcus, and Malassezia, focusing on the diseases they cause, their origins, how they spread, and the lab techniques we use to identify them

Yeast Pathogens

Ubiquitous Nature: Yeasts are single-celled fungi found everywhere – in the environment, on our skin, and in our bodies. Most are harmless, but some can cause serious infections, especially in immunocompromised individuals
Opportunistic Infections: Many yeast infections are opportunistic, meaning they occur when the immune system is weakened or the normal balance of microorganisms in the body is disrupted
Key Genera: We’ll focus on Candida, Cryptococcus, and Malassezia, which are the most clinically significant yeast pathogens

Candida spp.

Etiology: Candida species are the most common cause of fungal infections worldwide. Candida albicans is the most frequent culprit, but other species like C. glabrata, C. parapsilosis, C. tropicalis, and C. auris are increasingly important
Epidemiology
- Candida is part of the normal human flora, found in the mouth, gastrointestinal tract, and vagina
- Infections are often endogenous (arising from the patient’s own flora) but can also be acquired from healthcare settings
- Risk factors include:
  - Immunosuppression (HIV/AIDS, organ transplantation, chemotherapy)
  - Broad-spectrum antibiotic use
  - Central venous catheters
  - Surgery
  - Diabetes
  - Prolonged hospitalization
Transmission
- Not typically transmitted from person to person (except for C. auris, which can spread in healthcare settings)
- Infections usually arise from the patient’s own Candida flora when the immune system is weakened or the normal flora is disrupted
Disease States
- Mucocutaneous Candidiasis
  - Thrush: Oral candidiasis, characterized by white patches on the tongue and inner cheeks
  - Esophagitis: Candida infection of the esophagus, causing pain and difficulty swallowing
  - Vulvovaginal Candidiasis (Yeast Infection): Candida infection of the vagina, causing itching, burning, and discharge
  - Cutaneous Candidiasis: Candida infection of the skin, often in moist areas like the groin or underarms
- Invasive Candidiasis (Candidemia)
  - Candida infection of the bloodstream, a serious and potentially life-threatening condition
  - Can spread to other organs, causing infections in the heart (endocarditis), brain (meningitis), kidneys, liver, and spleen
- Chronic Disseminated Candidiasis (Hepatosplenic Candidiasis)
  - Occurs in patients with leukemia who are undergoing chemotherapy
  - Characterized by abscesses in the liver and spleen
Laboratory Diagnosis
- Specimen Collection
  - Mucocutaneous: Swabs, scrapings, or biopsies from the affected area
  - Blood: Blood cultures for candidemia
  - Other: CSF, urine, tissue biopsies, depending on the site of infection
- Direct Microscopic Examination
  - Gram stain or KOH preparation to visualize yeast cells and pseudohyphae (elongated yeast cells that resemble hyphae)
- Culture
  - Inoculation onto Sabouraud Dextrose Agar (SDA) or other fungal media
  - Candida species typically grow rapidly, forming creamy, white colonies
- Identification
  - Germ Tube Test: C. albicans produces a germ tube (a short, hypha-like extension) when incubated in serum
  - Biochemical Tests: Carbohydrate assimilation tests to determine which sugars the yeast can utilize
  - Chromogenic Agar: Specialized media that produce different colors for different Candida species
  - MALDI-TOF MS: Rapid and accurate identification based on protein profiles
  - Molecular Methods: PCR and sequencing for definitive identification
- Antigen Detection
  - Beta-D-Glucan assay to detect a component of the Candida cell wall in blood
- Antifungal Susceptibility Testing
  - Essential for guiding therapy, especially for non-albicans Candida species
  - Methods: Broth microdilution, Etest

Cryptococcus spp.

Etiology: Cryptococcus neoformans and Cryptococcus gattii are the primary pathogenic species
Epidemiology
- C. neoformans is found worldwide in soil contaminated with bird droppings (especially pigeon droppings)
- C. gattii is found in tropical and subtropical regions, associated with certain trees (e.g., eucalyptus)
- Infections are acquired through inhalation of spores
- Risk factors for C. neoformans infection:
  - HIV/AIDS (especially with low CD4 counts)
  - Organ transplantation
  - Use of corticosteroids or other immunosuppressants
- C. gattii can infect immunocompetent individuals
Transmission
- Not transmitted from person to person
- Acquired through inhalation of spores from the environment
Disease States
- Pulmonary Cryptococcosis
  - Lung infection, ranging from asymptomatic to pneumonia
- Cryptococcal Meningitis
  - Infection of the brain and meninges (membranes surrounding the brain and spinal cord)
  - A common cause of meningitis in HIV/AIDS patients
  - Symptoms: Headache, fever, stiff neck, confusion
- Disseminated Cryptococcosis
  - Infection that has spread to multiple organs, including the skin, bones, and prostate
Laboratory Diagnosis
- Specimen Collection
  - CSF: For suspected meningitis
  - Sputum: For suspected pulmonary infection
  - Blood: For disseminated infection
  - Tissue Biopsies: From skin lesions or other affected organs
- Direct Microscopic Examination
  - India Ink Stain: Used to visualize the capsule surrounding Cryptococcus cells in CSF. The capsule appears as a clear halo around the yeast cell
- Culture
  - Inoculation onto SDA or other fungal media
  - Cryptococcus species form mucoid (slimy) colonies
- Identification
  - Urease Test: Cryptococcus species are urease-positive (produce the enzyme urease)
  - Phenol Oxidase Test (Birdseed Agar): C. neoformans produces melanin when grown on birdseed agar, resulting in brown colonies
  - MALDI-TOF MS: Rapid and accurate identification
  - Molecular Methods: PCR and sequencing for definitive identification
- Antigen Detection
  - Cryptococcal Antigen (CrAg) Test: Detects Cryptococcus capsular polysaccharide antigen in CSF or serum. A highly sensitive and specific test for cryptococcosis
- Antifungal Susceptibility Testing
  - Recommended for all Cryptococcus isolates
  - Methods: Broth microdilution, Etest

Malassezia spp.

Etiology: Malassezia is a genus of lipid-dependent yeasts. Malassezia furfur is the most common species causing human infections
Epidemiology
- Malassezia is part of the normal skin flora of humans and other warm-blooded animals
- Infections are often associated with oily skin, sweating, and immunosuppression
Transmission
- Not typically transmitted from person to person
- Infections arise from the patient’s own Malassezia flora
Disease States
- Pityriasis Versicolor
  - A superficial skin infection characterized by hypo- or hyperpigmented patches, usually on the trunk and upper arms
  - More common in warm, humid climates
- Malassezia Folliculitis
  - Inflammation of hair follicles caused by Malassezia, often on the back and chest
- Seborrheic Dermatitis
  - A common skin condition characterized by scaly, inflamed skin, often on the scalp, face, and chest. Malassezia is thought to play a role in this condition
- Systemic Infections
  - Rare, but can occur in premature infants receiving intravenous lipid emulsions
Laboratory Diagnosis
- Specimen Collection
  - Skin Scrapings: For pityriasis versicolor and folliculitis
  - Blood: For suspected systemic infections in infants
- Direct Microscopic Examination
  - KOH preparation with or without staining (e.g., methylene blue) to visualize yeast cells and short, stubby hyphae (“spaghetti and meatballs” appearance)
- Culture
  - Malassezia species require lipid supplementation for growth
  - Culture media must be supplemented with olive oil or other lipids
  - Inoculation onto SDA with olive oil overlay
  - Malassezia species form small, creamy colonies
- Identification
  - Based on microscopic morphology and lipid dependence
  - MALDI-TOF MS and molecular methods can be used for definitive identification
- Antifungal Susceptibility Testing
  - Not routinely performed

Key Takeaways

Candida, Cryptococcus, and Malassezia are important yeast pathogens that can cause a variety of infections, ranging from superficial skin conditions to life-threatening systemic diseases
Accurate identification of yeast species is crucial for guiding appropriate antifungal therapy
Laboratory diagnosis involves a combination of direct microscopic examination, culture, biochemical tests, antigen detection, and molecular methods
Antifungal susceptibility testing is essential for managing infections caused by resistant strains

Key Terms

Yeast: A unicellular fungus that reproduces by budding or fission
Pseudohyphae: Chains of elongated yeast cells that resemble hyphae but are formed by budding rather than true hyphal growth
Germ Tube: A short, hypha-like extension produced by Candida albicans when incubated in serum
Capsule: A polysaccharide layer surrounding the cell wall of certain bacteria and fungi, such as Cryptococcus neoformans
India Ink Stain: A negative stain used to visualize the capsule of Cryptococcus neoformans in CSF
Lipid-Dependent: Requiring lipids (fats) for growth. Malassezia species are lipid-dependent yeasts
Pityriasis Versicolor: A superficial skin infection caused by Malassezia furfur, characterized by hypo- or hyperpigmented patches
Opportunistic Infection: An infection that occurs when the immune system is weakened or the normal balance of microorganisms in the body is disrupted
Candidemia: Candida infection of the bloodstream
Cryptococcal Meningitis: Infection of the brain and meninges caused by Cryptococcus neoformans
Antifungal Susceptibility Testing: Laboratory tests to determine the susceptibility of fungi to antifungal drugs
Azoles: A class of antifungal drugs that inhibit the synthesis of ergosterol, a component of the fungal cell membrane
Polyenes: A class of antifungal drugs that bind to ergosterol in the fungal cell membrane, disrupting its function
Echinocandins: A class of antifungal drugs that inhibit the synthesis of beta-glucan in the fungal cell wall

Major Pathogens

Dimorphic Fungi