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Whole Allergen

m208 Chaetomium globosum

m208 Chaetomium globosum Scientific Information

Type:

Whole Allergen

Display Name:

Chaetomium globosum

Route of Exposure:

Inhalation

Family:

Chaetomiaceae

Species:

globosum

Latin Name:

Chaetomium globosum

Summary

Chaetomium globosum is a hydrophilic mold with a worldwide distribution that is commonly found in water damaged buildings. C. globosum produces several well described mycotoxins. It is a sporadic cause of infectious mycosis in humans. It is also thought to be an important allergen in the pathogenesis of allergic respiratory disease associated with living and working in damp buildings. There are no recognized C. globosum specific allergens and the degree of cross-reactivity with other fungal and non-fungal allergens is yet to be determined. 

Allergen

Nature

Chaetomium globosum is a saprophytic ascomycete fungus. It is commonly found in soil and plant debris and has a worldwide distribution (1). C. globosum is one of the most common fungi isolated from wet cellulosic building materials (2). It is a thermotolerant fungus that produces grayish-brown, woolly colonies, with coiled setae and brown, subglobose ascospores (1). However, morphological diversity within the species has presented challenges to identification and taxonomy (3).

C. globosum is an infrequent cause of infection in humans (phaeohyphomycosis), although it is suggested that incidence is underestimated (1). Cases of cerebral, pulmonary and disseminated C. globosum mycoses have been reported in immunocompromised and drug-dependant patients. It is also an occasional cause of non-dermatophyte onychomycosis (4). There has also been interest in the secondary metabolites of C. globosum and their use in agriculture, industry and medicine (3). However, there is increasing evidence that these secondary metabolites are allergenic and cause significant mold-associated respiratory disease (5). 

Taxonomy

Taxonomic tree of Chaetomium globosum (6)

Domain

Eukaryote

Kingdom

Fungi

Phylum

Ascomycota

Class

Sordariomycetes

Order

Sordariales

Family

Chaetomiaceae

Genus

Chaetomium

Taxonomic tree of Chaetomium globosum (6)

Epidemiology

Worldwide distribution 

C. globosum is found worldwide, most commonly colonizing soil, straw, seeds, cereals, cardboard, paper, cotton, foam and fabric. The percentage of patient sera positive to a group of molds associated with building damp is broadly proportional to their occurrence in buildings, in contrast to fungal species for which exposure is universal, such as Aspergillus fumigatus and A. alternata (2).

A study from West Virginia, where one of the highest hospitalization rates for asthma in pediatric patients in the US is reported, measured the prevalence of hypersensitivity to C. globosum amongst patients with atopy (n=102). They found that 21% of patients reacted to one or more fungal allergens and that 7% of patients were sensitive to C. globosum (7). C. globosum was among a series of novel fungal challenges that the researchers used in parallel with a routine allergy-testing panel. The study demonstrated that 19% of fungal hypersensitivities would have been missed if the standard panel had been used alone. Similarly, a study from Poland has found 7% of a cohort of atopic patients were sensitized to C. globosum (8).

Environmental Characteristics

Living environment

C. globosum has been isolated from soil, animal dung, food, paper, textiles, plywood, carpet, wallpaper and wet walls (1). However, it is thought to be its capacity to colonize cellulose-based building material, such a gypsum boards, that is key to its ubiquity in water-damaged and damp homes (5). The profile of indoor fungal species varies across the United States. However, specific fungal genera appear to be ubiquitous, including Chaetomium (7). 

Route of Exposure

Main

Although direct evidence of aerosolized fungal fragments and respiratory disease is yet to be demonstrated, it is proposed that C. globosum is the cause of allergic disease through inhalation of specific allergen (7).

Clinical Relevance

There is consensus in the literature from epidemiological studies conducted in Europe, Canada and the USA that exposure to mold allergens has a significant health impact on people living and working in damp buildings. With an increased risk for respiratory symptoms, including asthma, hypersensitivity pneumonitis, and rhinosinusitis. Furthermore, indoor dampness and mold increase the risk of hypersensitivity to other allergens, such as house dust mites and pollen (5). It is estimated that between 10 and 30% of homes in North America have damp-associated mold problems, resulting in significant health and economic burden (2). However, no reported occupational risk is associated with this C. globosum (9).

Molecular Aspects

Allergenic molecules

Currently, no allergens are recognized by the WHO/IUIS Allergen Nomenclature Sub-committee. However, identifying allergens from fungi that grow on building materials is a priority for the US National Academy of Sciences panel on asthma, indicating the scale of the public health risk posed (2).

Mycotoxins associated with food and agriculture are well described; however, there is relatively little in the literature about mycotoxins in damp buildings. Several mycotoxins produced by C. globosum have been the focus of interest as potential allergens. C. globulosum strains from Canada produce chaetoglobosins A, C and F, chaetomugilin D; and chaetoviridin A with other chaetoglobosins and azaphilones in smaller amounts. Chaetoglobosin A and Chaetomugulin D have been studied in the mouse alveolar macrophage cell line, where an inflammatory effect has been demonstrated with upregulation of chemokine TNF-α (5). Furthermore, C. globosum inoculation on gypsum board results in chaetoglobosins A and C production as high as 50 µg/cm2 (10).

C. globosum produces a range of intracellular and extracellular antigens. C. globosum enolase is a 45–50 kDa enzyme with a role in fungal glycolysis. It is an immunodominant antigen secreted during hyphal growth by various fungal species, including Saccharomyces cerevisiae, Candida albicans, Cladosporium herbarum, Curvularia lunata, Alternaria alternata, Penicillium citrinum, Rhodotourla mucilaginosa, Aspergillus versicolor and Aspergillus fumigatus (10).

Furthermore, high molecular weight C. globosum chitinases (45 kDa and 47 kDa [Chg47]), identified by ELISA and immunoblotting tests, have been shown to be allergenic (2). A Chg47 monoclonal antibody assay can be used to identify C. globosum in house dust spores and is a potential tool for allergen exposure assessment (8). 

Cross-reactivity

In the study on patients with atopy from West Virginia, researchers noted multiple IgE reactive bands on immunoblotting that were not inhibited by other common aeroallergens. The authors concluded that further work was required to determine cross-reactivity between the fungal species studied (7). 

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Christian  Fischer

 

Last reviewed: January  2022

References
  1. Capoor MR, Agarwal P, Goel M, Jain S, Shivaprakash MR, Honnavar P, et al. Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review. Mycoses. 2016;59(3):186-93.
  2. Provost NB, Shi C, She Y-M, Cyr TD, Miller JD. Characterization of an antigenic chitosanase from the cellulolytic fungus Chaetomium globosum. Medical Mycology. 2013;51(3):290-9.
  3. Wang XW, Houbraken J, Groenewald JZ, Meijer M, Andersen B, Nielsen KF, et al. Diversity and taxonomy of Chaetomium and chaetomium-like fungi from indoor environments. Studies in Mycology. 2016;84:145-224.
  4. Aspiroz C, Gené J, Rezusta A, Charlez L, Summerbell RC. First Spanish case of onychomycosis caused by Chaetomium globosum. Medical Mycology. 2007;45(3):279-82.
  5. Miller JD, McMullin DR. Fungal secondary metabolites as harmful indoor air contaminants: 10 years on. Appl Microbiol Biotechnol. 2014;98(24):9953-66.
  6. Life Co. Chaetomium globosum Kunze 2021 [cited 2022 06.01.22]. Available from: https://www.catalogueoflife.org/data/taxon/69PDR.
  7. Beezhold DH, Green BJ, Blachere FM, Schmechel D, Weissman DN, Velickoff D, et al. Prevalence of allergic sensitization to indoor fungi in West Virginia. Allergy Asthma Proc. 2008;29(1):29-34.
  8. Shi C, Provost NB, Desroches T, Miller JD. Quantification of C. globosum spores in house dust samples. Ann Agric Environ Med. 2014;21(3):525-30.
  9. Madsen AM, Crook B. Occupational exposure to fungi on recyclable paper pots and growing media and associated health effects – A review of the literature. Science of The Total Environment. 2021;788:147832.
  10. Green BJ, Nayak AP, Lemons AR, Rittenour WR, Hettick JM, Beezhold DH. Production of a Chaetomium globosum Enolase Monoclonal Antibody. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy. 2014;33(6):428-37.