Candida albicans- An Overview

Habitat of Candida albicans

• Normal Habitat: mucosal membranes of human and other warm blooded animals.
• Also found in the gut, the vagina or also in the surface of the skin.
• Found in the digestive tract of birds also.
• Isolated from soil, animal, hospitals, in-animate objects and food.
• Worldwide distribution

Morphology of Candida albicans

• Small, oval, measuring 2-4 µm in diameter.
• Yeast form, unicellular, reproduce by budding.
• Single budding of the cells may be seen.
• Both yeast and pseudo-hyphae are gram-positive.
• Encapsulated and diploid, also form true hyphae.
• Polymorphic fungus (yeast and pseudohyphal form)
• Can form biofilms
• Normal condition: Yeast
• Special condition (pH, Temperature): Pseudohyphae
• 80-90% of cell wall is carbohydrate

Cultural Characteristics of Candida albicans

SDA

• Creamy, pasty colonies, smooth after 24-48 hours at 25-37°C
• Yeast smell (odour)

Blood Agar

• White creamy colored
• Foot-like extensions from the margin.

PDA

• Smooth creamy colonies after 24-48 hours

CHROMAGAR

• Green colonies

Life Cycle of Candida albicans

• Asexual and doesn’t perform meiosis
• Ability to grow with three distinct morphologies- yeast, pseudo-hyphae and true hyphae
• Para-sexual life cycle
• Switch between different phenotypes
• Efficient mating requires the diploid cells of opposite mating types first to switch from the more common “white” phase to the “opaque” phase and then undergo cell fusion.
• The resulting tetraploid strains can return to the diploid state via a non-meiotic parasexual program of concerted chromosome loss.
• White form: white and rounded cells forming dome-shaped colonies
• Opaque form: opaque, elongated cells forming a flatter colony.
• Opaque form is more efficient for mating than the white form

Pathogenesis of Candida albicans

• Opportunistic fungal pathogen that causes candidiasis in human
• Occurs in immunocompromised peoples such as HIV infected, transplant recipients, chemotherapy patients, etc.
• Mode of transmission:
  • Mother to infant through childbirth
  • Rarely through sexual contact
  • People to people transmission in hospital settings

Virulence Factors of Candida albicans

1. Polymorphism

• Yeast, pseudohyphae and hyphae
• Hyphae is more important for infection

2. Adhesins (Als 3 Protein)

• Sets of glycosylphatidylinositol (GPH)- linked cell surface glycoproteins that allow it to the surfaces of microorganisms
• Helps with biofilm formation also

3. Invacins (Als 3 Protein)

• Helps with the invasion of C. albicans into host epithelial and endothelial cells.
• Ssa1 codes for heat shock protein
• Induces host cells to engulf the fungal pathogens
• Invasion by the active penetration of C. albicans into host cells by involving hyphae.

4. Biofilm Formation

• Yeast cells à adherence à surface à development of hyphae cells à in the upper part of biofilm à leads to a more resistant mature biofilm à dispersion of yeast cell.
• Bcr1, Tec1 and Efg1 function as important transcriptional factors.

5. Secreted hydrolases

• 3 main classes of hydrolases: proteases, phospholipases and lipases
• Helps in active penetration into host cells
• Helps in uptake of extracellular nutrients from the environment.
• 10 proteases (Sap 1-10), 4 major classes (A, B, C and D) of phospholipases and lipases consist of 10 members (LIP 1-10).

6. Metabolic Adaption

• In the process of infection, it undergoes metabolic adoption such as their glycolysis, gluconeogenesis and starvation responses.
• Example: quickly switch from its glycolysis to starvation responses with the activation of glyoxylate cycle.
• Due to this, it can infect almost any organ through the blood stream.

Stages of Infection

1. Colonization

• Epithelial adhesion
• Nutrient acquisition

2. Superficial Infection

• Epithelial penetration
• Degradation of host protein

3. Deep-Seated Infection

• Tissue penetration
• Vascular invasion
• Immune evasion or escape

4. Disseminated Infection

• Endothelial adhesion
• Infection of other host tissues
• Activation of coagulation and blood clotting cascades.

Types of Candidiasis

Mucosal Candidiasis

• Oral candidiasis: mucous membrane of mouth
• Denture related stomatitis: mild inflammation and redness of oral mucous membrane beneath a denture.
• Angular cheilitis: inflammation of one or both corners of the mouth
• Median rhomboid glossitis: redness and loss of lingual papillae
• Vulvovaginitis: white lesions on the epithelial surfaces of vulva, vagina and cervix
• Balanitis: infection of glans penis
• Esophageal candidiasis: infection of esophagus painful swallowing.

Cutaneous Candidiasis

• Candida folliculitis: infection and inflammation of hair follicles, rash may appear as pimples.
• Candidal intertrigo: infection of skin located between intertriginous folds of adjacent skin.
• Candidal paronychia: inflammation of the nail fold.
• Perianal candidiasis: irritation of the skin at the exit of the rectum.
• Chronic mucocutaneous candidiasis: immune disorder of T cells, deficient of CMI.
• Congenital cutaneous candidiasis: skin condition in new borne babies caused by premature rupture of membranes together with a birth canal infected with C. albicans.
• Diaper candidiasis: infection of a child’s diaper area.
• Erosio interdigitalis blastomycetia: characterized by an oval shaped area of macerated white skin on the web between and extending onto the sides of the fingers.
• Candidal onychomycosis: nail infection

Systemic Candidiasis

• Candidemia: leads of sepsis
• Disseminated candidiasis (organs)
• Endocarditis
• Gastro intestinal tract infection
• Respiratory tract infection
• Genitourinary candidiasis
• Hepatosplenic candidiasis (Chronic Disseminated Candidiasis)

Lab Diagnosis of Candida albicans

Specimens: Exudates, Tissues, Scrapings

1. Microscopy (Scraping)

• Examined in wet film in 10% KOH
• Visualization of pseudohyphae and budding yeast cells of candida
• Gram staining: Gram positive (+ve)

2. Culture

• SDA: Creamy white, smooth colonies
• CHROMAGAR: Green colonies

3. Identification of albicans

• Germ Tube Test: produce germ tube test within 2 hours when incubated in human serum at 37°C.
• Chlamydospores: produced by C. albicans on corn meal/rice agar at 25°C. They produces round thick walled chlamydospores borne terminally or laterally.
• Biochemical Tests: Glucose and maltose fermented with acid and gas production, sucrose and lactose not fermented, Pale pink coloration in Tetrazolium reduction medium

4. Serology

• Limited specificity
• Serum antibodies and cell mediated immunity are demonstrable in most people because of life long exposure to C. albicans.
• C. albicans antigen is a delayed hypersensitivity skin test, which is used as an indicator of functions of the CMI.
• ELISA and RIA: detection of circulating Candidial antigen either cell wall mannan or cytoplasmic constituents.

5. 1,3-beta-D-glucan assay

• Beta-D-glucan is a component of the cell wall of fungi.
• Detected by its ability to activate factor G of the horse-shoe crab coagulation cascade.
• Highly specific and sensitive test.

6. DNA probe and PCR

Treatments of Candida albicans

1. Oral candidiasis: Nystatin, miconazole, amphotericin B.
2. Cutaneous candidiasis: Clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, nystatin.
3. Systemic and oral azoles: Fluconazole, itraconazole or posaconazole.
4. Vulvovaginitis: single dose of oral fluconazole, topical antifungals (butoconazole, clotrimazole, miconazole, nystatin, ticonazole, terconazole).
5. Blood infections: intravenous fluconazole or an echinocandin (caspofungin)
6. Candidemia: Fluconazole and Anidulafungin

Prevention and Control of Candida albicans

• Keep healthy life style
• Good hygiene, proper nutrition, careful antibiotic use.
• Add probiotics, reduce sugar intake
• Wear cotton underwear and loose pants
• Change immediately wet clothes