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Whole Allergen

m5 Candida albicans

m5 Candida albicans Scientific Information

Type:

Whole Allergen

Display Name:

Candida albicans

Route of Exposure:

Inhalation

Family:

Saccharomycetaceae

Species:

Candida albicans

Latin Name:

Candida albicans

Summary

Candida albicans (C. albicans) is a unicellular yeast. Besides its allergenic potential, it is an opportunistic pathogen in immunocompromised individuals. C. albicans has three distinct growing features - yeast, pseudo-hyphae, and true hyphae. The cell wall of the fungus is a complicated, multi-faceted, solid structure made up of mannoproteins, β-glucans, and chitin. C. albicans is thermotolerant and a part of normal human microbiota, found at mucosal sites in healthy individuals. They grow in colonies, which are white in color with smooth and creamy texture. C. albicans can adapt and proliferate in various host environments. Ideal environmental conditions for C. albicans hyphal growth are 37°C temperature, presence of serum, neutral pH, and high CO2. In sensitized individuals, C. albicans can induce or worsen life threatening asthma and skin symptoms and atopic dermatitis. Major allergens identified are Cand a 1 and Cand a 3. Cross reactivity of C. albicans allergenic molecules is reported with molds and yeast.

Allergen

Nature

Candida albicans (C. albicans) is a yeast and one of the most common indoor and outdoor fungi. Candida are rarely detected as airborne spores (1). Candida spp. are unicellular organisms of size 4-6 μm, ovoid in shape with thin wall called blastospores. They reproduce by budding (2). 

Habitat

C. albicans is the major fungus identified among Candida spp. (3). It is usually a harmless commensal organism and a normal part of the human microbiota. In healthy individuals, C. albicans is found in low numbers at mucosal sites, e.g., oral, gastrointestinal (GI), genital, and airway (4, 5). Soil and organic debris also contain Candida spp. (1).

Taxonomy

There are some 200 species of Candida, categorized as albicans and non-albicans. Around 90% of invasive candidiasis is caused by five different Candida species, including C. albicans C. parapsilosis, C. tropicalis, C. glabrata, C. krusei (2, 6). 

Taxonomic tree of Candida albicans (1)
Domain Eukaryota
Kingdom Fungi
Phylum Ascomycota
Subphylum Mucoromycotina
Class Saccharomycetes
Order Saccharomycetales
Family Saccharomycetaceae
Genus Candida
Species Candida albicans
Taxonomic tree of Candida albicans (1)

Tissue

C. albicans has three distinct growing features - yeast, pseudo-hyphae, and true hyphae (3). Microscopic evaluation showed yeasts can exist in the form of pseudohyphae i.e., budding cells, which do not separate, or true hyphae (multicellular organisms). They grow in colonies in agar and the colonies are smooth and creamy in texture with white color (2). The cell wall of the fungus is a complicated, multi-faceted, solid structure made up of mannoproteins, β-glucans, and chitin that protects the fungus from the surrounding and gives rigidity and shape (7).

Epidemiology

Worldwide distribution

Candida species are associated with immediate or delayed-type hypersensitivity (DTH). The former occurs mainly as asthma or AD, while the latter can be used to evaluate cell mediated immunity in a given patient. In 200 Tanzanian children of preschool age, DTH to C. albicans was inversely associated with infectious disease (8).

Candida spp. is the most important agent causing opportunistic mycoses globally, responsible for 72.8 cases/million/year with 33.9% case/fatality ratio worldwide (3, 6). C. albicans is also the most common species responsible for invasive candidiasis (66% of all the Candida spp.) throughout the world (6). In HIV patients, the prevalence of oral candidiasis due to C. albicans correlates with the degree of immunosuppression (9).

 Candida species, especially C. albicans, may cause hospital-acquired bloodstream infections (BSI) with variable frequency worldwide, from 37% in Latin America to 70% in Norway. It is the 4th leading cause of nosocomial BSI in the United States (US), responsible for 8-10% of all hospital-acquired BSIs and considered as the second most common cause of death from such infections in the US (6, 9, 10). 

Risk factors

Sino-nasal polyposis increases the risk of hypersensitivity to C. albicans (1). On the infectious side, low neutrophil counts, post-surgical breaches in GI tract, use of broad-spectrum antibiotics, corticosteroids, central venous catheters, parenteral nutrition, prolonged ICU stay, invasive ventilation, and Candida spp. colonization at different body sites are risk factors for the development of candidemia (5, 9). 

Environmental Characteristics

Living environment

C. albicans can adapt and proliferate in various host environments (7). C. albicans ideal environmental conditions for hyphal growth (providing the main virulence factors) are 37°C temperature (thermotolerant), presence of serum, neutral pH, high CO2. Yeast growth takes place at 30°C and in acidic pH (pH 4), while pseudo-hyphal growth takes place at 35°C and at pH 5.5 (3). In healthy individuals the density of C. albicans on mucosal surfaces depends on the hormonal status, stress, innate or adaptive immunity, and composition of the microbiota (4). Higher relative abundance of Candida spp. in stool samples from neonates has been associated with an increased risk for asthma and atopic disease at preschool age (11). 

Worldwide distribution

C. albicans is found worldwide and is usually the most commonly isolated Candida species. Nonetheless, there has been an increase toward non-albicans species worldwide in the last 15 years. Among various Candida spp. (such as C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis), the proportion of C. albicans isolates in selected studies on candidemia globally in different years are as follows: 38% in USA (2012), 37.6% in Latin America (2013), 45.4% in Spain (2014), 20–55% in Asia-Pacific region (2016), and 56% in France (2014) (2). 

Route of Exposure

Main

Inhalation is the primary route of exposure, however it is still controversial whether inhalation of this mold causes allergenicity (12).

 

Clinical Relevance

C. albicans, although a normal component of human microbiota, can cause hypersensitivity diseases in healthy individuals due to its ability to activate Th 1, Th 2 and Th17 responses (4, 13). Candida spp. elicits IgG responses in normal subjects (14), and type II hypersensitivity reactions in some patients, such as those showing reactions against the mannan-polysaccharide present in Candida cell wall (15).

Asthma

Mold-sensitized individuals are more predisposed to developing life threatening asthma (4). A study by Khosravi et al. (2009) extracted the C. albicans antigens and evaluated the specific anti-Candida IgE in the sera of 95 atopic dermatitis (AD), 85 asthmatic patients, and 70 non-atopic individuals (controls). Sensitization to C. albicans was present in 52.6% of AD patients and 54.1% of asthmatic patients versus 4.3% of controls. In AD patients, predominant allergens were found at the 25, 34, and 57 kDa protein bands, only partially overlapping with major allergens 22, 25, and 34 kDa in asthmatic patients. The study indicated that C. albicans may produce various allergenic components, which can lead to allergic reactions and may be important pathogenetically for AD and asthma patients (16).

Atopic Dermatitis

Fungi are considered to be important allergen sources in individuals with atopic disease. C. albicans colonizing the GI tract can induce or aggravate atopic dermatitis (AD), asthma, and other atopic diseases (4, 11). Diabetic patients may develop skin candidiasis, while immunocompromised patients are at greater risk for sepsis (1). Chronic exposure to C. albicans may aggravate AD in atopic and allergic individuals (5).

A study by Savolainen et al. (1993) evaluated the association between C. albicans exposure and sensitization with AD symptoms among 156 allergic individuals. The results showed a statistically significant association between C. albicans sensitization and AD symptoms in sensitized individuals exposed to C. albicans (17).

Other diseases

Candida infections can involve skin (intertrigo, wound infections), mucous membranes (oropharyngitis, esophagitis, and vulvovaginitis), and lower urinary tract (18). C. albicans can cause painful mucosal infections, which includes vaginitis in women or oropharyngeal thrush (in HIV + patients), and also severe life-threatening blood/systemic infections in vulnerable patients (3).

Mucosal infections: C. albicans can cause thrush, identified as white spots, which underlines the inflammation site, also known as pseudomembranous candidiasis. Common locations comprise vaginal (vulvovaginal candidiasis), oral and pharyngeal (oropharyngeal candidiasis), esophageal, and GI mucosae (gastrointestinal candidiasis) (3).

Systemic infections: Candida spp. are also reported to cause hospital acquired blood stream infections, and the incidence of nosocomial candidiasis may range from 3% to 15% depending on the hospitals (9). Mortality rate of invasive candidiasis ranges from 40-60%, and may increase above 60% when complicated with septic shock (18). In immunocompromised individuals, C. albicans can induce systemic infections affecting the cardiovascular system, bones, and brain (5).

Molecular Aspects

Allergenic molecules

Till date, two allergenic molecules have been identified and characterized and published officially by World Health Organization/International Union of Immunological Studies (WHO/IUIS) Allergen Nomenclature Sub-Committee for C. albicans (19).The table below provides detailed information on each of the allergenic protein identified by WHO/IUIS as of 27th January, 2021:

Allergens Molecular Weight (kDa) Biochemical name Allergenicity
Cand a 1 (Major) 40 Alcohol dehydrogenase
  • Reactivity on IgE immunoblots was found in 77% of 30 asthmatic patients with a positive skin test and/or RAST (20).
Cand a 3 (Major) 29 Peroxisomal membrane protein
  • IgE binding prevalence of 64% (21).
  • IgE binding reactivity showed in 56% of 16 sera of asthmatic patients with a positive IgE test to C. albicans (21).
Allergens Molecular Weight (kDa) Biochemical name Allergenicity

kDa: kilodaltons, RAST: Radioallergosorbent, IgE: Immunoglobulin

Other 16 minor allergens with a molecular weight ranging from 20 to 94 and 16 to 135 kDa are also identified (16). A 46 kDa enolase protein of, named Cand a enolase, is another allergen with a prevalence of 37% in 54 patients allergic to C. albicans (22). Other proteins like acid protease (Cand a CAAP, 44 kDa), aldolase (37 kDa), phosphoglycerate kinase (43 kDa), cyclophilin (Cand a Cyp, 18 kDa) and even a heat shock protein (Cand a HSP90, 90 kDa) are also reported as allergens of C. albicans. (12, 21). However, these molecules are not yet officially listed by WHO/IUIS.

Cross-reactivity

C. albicans allergenic compounds of molecular weight 18, 24, 26, 34, 38 and 48 kDa have shown cross reactivity with the yeast Pityrosporum orbieular (23). Allergenic molecules such as Cand a 3, Cand a CyP, and Cand a enolase are cross reactive to fungal spp. from the same phylum (12).

Aspergillus fumigatus allergen Asp f 12, (a HSP90 protein) shows remarkable homology to the HSP90 heat shock protein of C. albicans, but also to HSP90 from S. cerevisiae, Trypanosoma, housefly, mouse, and Homo sapiens. In inhibition experiments, cross reactivity was observed between the allergen enolase of C. albicans (Cand a enolase), A. alternata, C. herbarum, and A. fumigatus (12).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

 

Last reviewed: February 2021

References
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