Chaetomium spp.

Chaetomium spp. on gypsum boardChaetomium spp. on woodChaetomium spp. on a ceiling tileChaetomium spp. on EM agarChaetomium spp. on RB agarChaetomium spp. - StereoscopyChaetomium spp. - Microscopy (EM Culture)

Basics

Taxonomy

Kingdom Fungi Order Sordariales
Phylum Ascomycota Family Chaetomiaceae
Class Euascomycetes Genus Chaetomium

The genus Chaetomium comprises between 80 and 100 species, depending on the consulted documents: taxonomic data vary greatly for this genus {3318}. Chaetomium globosum is the best known and studied species {767}. Some of the most common ones are Chaetomium atrobrunneum, Chaetomium funicola, Chaetomium globosum, and Chaetomium strumarium.

Habitat/Ecology

Chaetomium are common fungal species with a worldwide ubiquitous distribution and are widespread in soil and on decaying plant materials {724, 741} but spore concentrations in outdoor air are not very high {1175, 3314}. Indoors, these fungi live on cellulose, and are found on wood, compost, sheet rock, straw, and similar materials. It is also known as a soft-rot fungus for softwood and hardwood timber {724}.

Chaetomium are also found indoors on a variety of substrates containing cellulose, including document archives, wallpaper, textiles and construction materials {989}.

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They have even been isolated from degraded polyimide coatings, showing extensive colonisation, and first studies indicate that this fungus may cause breakdown of plastics and polymers {3358}.

In cold climates, this fungus can take as long as three weeks to mature. Spores are formed inside fruiting bodies named perithecia. At maturity or by mechanical disturbance, the perithecia break up, and spores are forced out and spread by wind, insects and water splash.

Growth requirements

Some Chaetomium grow well between 16 and 25°C, and most species grow best between 25 and 35°C. A few species being thermotolerant or thermophilic {1872}; in fact, those that have been reported to cause invasive human diseases grow also well between 35 and 37°C {737}.

In fact, according to the optimal growth temperature when cultivated on Malt Agar with 2% yeast extract, one can distinguish several groups of Chaetomium: mesophilic (15 35°C), semi-mesophilic (15-37°C), microthermophilic (15-40°C), thermotolerant (15 45°C) and thermophilic (25-55°C) {3363}.

The thermal point of mortality of the species C. globosum is of 55-57°C. On the other hand, ascospores are even more resistant to environmental conditions: they can survive at 60°C for 60 minutes {767}. In vitro, on Sabouraud Agar medium, they show a slight heat resistance, surviving at 60°C for 60 minutes, but not at 70°C for 10 minutes as other soilborne microfungi can {2497}. Their ascospores may germinate at temperatures in the 4-10°C to 38°C range, optimally at 24-28°C {989}.

C. globosum will grow best at a pH between 7,1 and 10,4, but may also grow at pH of 3,5 11 {989}. Chaetomium sp. requires a water activity (Aw – available water) higher than 0,90 for growth {876, Andersen, B., 2000}, optimally 0,94 {989, 724}. Because of this requirement, Chaetomium sp. is regarded as a tertiary coloniser, like others high Awfungi such asStachybotrys, Alternaria, Fusarium and Ulocladium {603}.

Water Activity: Aw = 0.91-0.94

Growth on building materials or indoor environment

Chaetomium spp. grow well on most cellulose containing building materials in water damaged buildings {3289}. These cellulolytic fungi are widespread and very commonly found on damp sheetrock paper. Several Chaetomium species are very common in indoor environments: C. elatum, C. globosum and C. murorum {1872}.

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Assessment studies done inside homes and public buildings, by air {1527, 1528} and surface {1175} and settled dust sampling {550}, have found Chaetomium prevalent under many latitudes and climates {635, 199, 1175}.

In indoor environment, isolates of Chaetomium were reported found in house dust {1829}, growing on damp building materials containing cellulose-based materials (such as wood, wallpaper and cardboard) affected by leaking water; Chaetomium is reported as one of the most frequent fungal genus in those conditions, often ranking in third position afterPenicillium spp. and Aspergillus spp. {767, 605, 876, 550, 807, 1527}.

On artificially infested building materials, Chaetomium’s development is very fast, covering the surface with substantial growth after two weeks {603}. However, since the spores are cemented together by mucilage and are also trapped by hairs, few become airborne until the mould has completely dried out or is mechanically disturbed during renovations or mould remediation. It is, therefore, not uncommon to find low Chaetomium spore counts in pre-remediation air samples and relatively higher counts in post-remediation samples {3313}.

When dealing with indoor contamination, in particular when dealing with cases of sick building syndrome related fungi, fumigation treatment with chloride dioxide has some fungicidal effects on Chaetomium, but strains of this species appeared to be more resistant than Stachybotrys chartarum and Penicillium chrysogenum {732}.

 

Laboratory section

Normal laboratory precautions should be exercised in handling cultures of this species within Biosafety Level 2 practices and containment facilities.

Colony, macroscopic morphology

The surface of the colony is spreading, cottony, usually white, becoming tannish gray or greyish olive with age. The reverse in usually orange-tan tinted with red but may be brown to black {412}. On Malt Agar medium, colonies have a granular aspect, green-dark with black reverse. On Czapek, colonies are translucent white with a colourless reverse. On CYA medium, they are filamentous, granular, greyish in the center, green towards the outskirt. The reverse is dark-red in the center, green-black on outside {989}. Cultures have a strong “musty” or “mildew” odour.

Chaetomium grows and sporulates on general fungal media. Growth is quite rapid {415}, colonies on Oatmeal Agar at 24°C attain a diameter of 5.0 7.0 cm in 10 days. Chaetomium may need 8-20 days for fruiting body production and sporulation: at maturity, the fungal mat consists of a dense layer of fruiting bodies {724}.

Microscopic morphology

The thallus is made up of septate hyphae, hyaline to light brown in colour. Among the septate hyphae, large flask-shaped fruiting bodies (perithecia) are easily seen (100-150 x 110-225 µm) on most media: they are best seen on Potato Dextrose Agar (PDA) on which they appear as dark-brown to blackish, globose to ovoid (egg-shaped) opaque structures surrounded with thick hair-like hyphal filaments called setae. These perithecia contain multiple sac-like structures (asci), each enclosing spores (ascospores). The dark setae can take a variety of forms, depending upon the species. They can be septate, unbranched, flexuous or even coiled, pigmented and rough-walled. Asci are stalked, club-shaped, containing 4 or 8 spores; the ascospores readily observed coming out of the perithecium, are brown, oval or have a distinctive lemon-shaped (9-11 x 7 8.5 µm) but may occur in a variety of sizes, shapes, and colours. The ascospores are very resistant to dry conditions and UV irradiation {2207, 412, 724}.

Specific metabolites

Organics compounds (including VOCs)

In pure culture, Chaetomium species produce many secondary metabolites and mycotoxins {876}; compounds such as enzymes, ergosterol, alkaloids {2522}, antibiotics (chaetocins, chaetomin, cochliodinol), and antifungal compounds have been often reported {767, 1772, 876, 1741}. Some of the other metabolites reported are: heptelidic acid, alternariol monomethyl ether, chaetomanone, chrysophanol, cochliodinol, and cytochalasane.

In a study of strains of indoor mouldy building provenance, exometabolites of Chaetomium were found active in vitro (6/14 strains) and showed some ciliostatic activity {767}:

However, the effects of Chaetomium mVOCs on humans exposed to contaminated building materials have not yet been studied.

Mycotoxins

Species of Chaetomium are known to produce many potent mycotoxins. Some of these are: chaetoglobosins, chaetoatrosin, chaetomanone, chaetochromins (A to D), chaetocin, chaetomin, cochliodinols, mollicellins and sterigmatocystins and O methylsterigmatocystin {746, 800}. Chaetochromins have reported as teratogen {1767}.The main toxins produced are chaetoglobosins (A to K) {727}; new chaetoglobosins (Q,R and T) have recently been added to those previously characterized {1744}.

Some Chaetomium species have been reported to produce sterigmatocystin which is a potent carcinogen {876}. Several species of Chaetomium produce mycotoxins when growing on vegetable matter and sometimes on building materials.

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Chaetomium globosum, C. mollipilium, C. rectum, and C. subaffine as well as C. cochliodes are known to produce chaetoglobosins. From cultures of C. thielavioideum, chaetocin, sterigmatocystin and O-methylsterigmatocystin were isolated {797}.

Chaetominine, a cytotoxic alkaloid, was characterized from a strain of Chaetomium sp. {726}. New metabolites are currently discovered, following screening of different strains; among these, immunosuppressive chetomin-related metabolites were discovered {1745}.

C. globosum produces high quantities of mycotoxins, especially chaetoglobosins A and C, even when growing on gypsum board {603, 767, 800}:even relatively low levels of these compounds have been shown to be lethal for various tissue culture cell lines {3289}. Species C. mollicelum and C. globosum produce mutagenic products called mollicellins, (C, D, E, and G){767, 1772, 1395, 727}.

Cytotoxic orsellinic acid esters (globosumones A-C) have been isolated from an endophytic strain of C. globosum {1739}.

Some studies have been conducted on the production of mycotoxins by Chaetomium spp. in the indoor environment {1395}. Chaetomium globosum, the most common species within this genus, produces chaetoglobosins A and C when cultured on building materials {3289}. In this study, out of 30 C. globosum isolates from water-damaged buildings cultured on OA media for 4 weeks, 16 produced detectable amounts of chaetoglobosin A, and every isolate produced chaetoglobosin C.

Airway toxic endometabolites and exometabolites, extractable from house dust with chloroform, have been linked to the presence of Chaetomium isolated from the same house dust {550, 767}.

Adverse health reactions

Health risks associated with mould exposure in water-damaged buildings are well established, especially for upper and lower respiratory tract symptoms. Chaetomium spp. are among the most prevalent moulds in this setting; Chaetomium could thus significantly contribute to different indoor air problems.

Irritation and inflammation

No report has been made concerning inflammation reactions in humans specifically due to Chaetomium exposure.

Nonetheless, this genus does produce many potentially irritant substances that could contribute to the reported health effects linked to the exposure to a mouldy environment. In general, a number of organic compounds of fungal origin, including volatile organic compounds (mVOCs), have been identified in indoor air in damp buildings: these are thought to contribute to different indoor air quality problems. Most of identified metabolites are non-reactive and found in low concentrations in the indoor air {594}.

Allergic reactions

Chaetomium sp. is reported to be allergenic {741}. Some species are linked to Type I allergies, hay fever and asthma {2342, 3095} as well as to allergic sinusitis. In one study of atopic patients, 7% of the subjects had positive skin tests for C. globosum {2255}.

More details

Even if Chaetomium, especially C. globosum, sensitisation is fairly prevalent, hypersensitivity reactions to the Chaetomium genus, in particular IgE-mediated reactions, have not been well studied. In spite of the fact that Chaetomium species produce airborne spores often found in spore counts, it appears that organisms in this genus seldom induce IgE-mediated reactions in sensitised individuals: It is not clear whether Chaetomium has an actual low allergenic potential or if this impression is the result of the lack of study of this fungus as an allergen {3364}.

Chaetomium has been associated with cases of asthma. A species of Chaetomium, C. umbratile, was reported isolated from house dust samples, in asthmatic patients’ dwellings {1829}. In a Brazilian study, evaluating sensitisation in patients with asthma and/or allergic rhinitis to 42 airborne fungi using skin specific IgE tests, 15/201 subjects were shown to be sensitised to Chaetomium allergens {3362}. In an other study, the moulds Chaetomium globosum, Aspergillus fumigatus, and the Eurotium group were the primary species found in the NC homes of asthmatic children {1527}.

In the differential diagnosis between allergic and non-allergic asthma, the addition of Chaetomium allergens to the standard battery of skin tests has proven to be useful, suggesting that Chaetomium allergy is under diagnosed {1759}.

Chaetomium globosum was amongst the fungi associated with allergic sinusitis in a study of teachers exposed to a mouldy environment. One study found an association between sinusitis and elevated mould-specific IgG levels for many species, including Chaetomium globosum {199}. The same Chaetomium exposure may also play a role in the human paranasal sinus infection or colonisation: in one case, histological examination following infundibulectomy showed necrotic material with hyphae of A. fumigatus and perithecia of Chaetomium sp. {1754}.

Allergic components and mechanism

No purified allergen fractions have yet been characterised.

Hypersensitivity pneumonitis

Type III hypersensitivity pneumonitides (HP) due specifically to Chaetomium have not yet been reported.

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However, complex fungal exposures are known to be associated with HP. One example is the complex ecosystem that can be found in a contaminated humidifier system: bacteria such as Klebsiella species and many moulds such as Aureobasidium, Chaetomium, Pullularia, Cephalosporium, Curvularia, and Penicillium species. In this particular instance, we do not know the extent of the contribution of Chaetomium antigens to the humidifier lung syndrome. Even in the context of a specific exposure, there can be several potential antigens that might be triggering the inflammatory lung disease {3360}.

Toxic effects (mycotoxicosis)

Chaetomium produce many highly toxic compounds under given sets of growth conditions. Relatively low levels of these compounds have been shown to be lethal to various tissue culture cell lines {1153, 746, 800}.

Some toxicity studies have been conducted on animals, but Chaetomium mycotoxicosis in humans has not been well studied. However, studies have shown contaminated cereals to be extremely toxic, even lethal, when fed to animals {1775, 1771, 1769,}.

Crude extracts of Chaetomium, studied in mice, have shown spleen, liver and kidney toxicity {1771}; in this model, the extracts have been associated with hemoglobinuria and hemorrhagic enteritis.

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Toxicity of C. globosum, using strains isolated from corn, was tested by feeding animals. The results indicate that isolates of this species, when grown on corn, are remarkably toxic to rats but harmless to swine. In this study, premortem symptoms lesions included hemoglobinuria and hemorrhagic enteritis {1775}.

A similar experiment was done with mice receiving intraperitoneally crude toxin from strains collected from maize and wheat fields. Chaetomium was found to be quite toxic, damaging kidneys, spleen and liver. In fact, in this particular study, among the different fungal contaminants showing 1+ toxicity, the Chaetomium spp. extracts were found to be the most toxic, damaging all 3 organs and causing 12.5% of mortality. {1771}. An other experiment using Chaetomium sp. from contaminated corn as a feed ingredient caused 100% mortality in broiler chicks {1769}.

Chaetochromin, a polyphenolic mycotoxin produced by Chaetomium sp., has proven to be teratogenic to mice embryos when administered orally to the mother {1767}.

On human cell lines, cytochalasin B, one of the many Chaetomium toxins, has proven to be a remarkably specific and potent inhibitor of D-glucose transport in human erythrocytes: this inhibition mechanism is explained to be a kinetically competition type {3361}.

Because of the high toxicity of ingested or injected Chaetomium extracts in animals and given the few conclusive studies on human cell lines, there are some concerns about the potential effects of indoor Chaetomium exposure. Some authors suggest that Chaetomium mycotoxins present indoors, could pose a risk to exposed occupants. The possible toxic effect of Chaetomium strains on the respiratory tract should not be underestimated in occupants of damp mouldy buildings {767} and long-term chronic exposure studies should be undertaken to assess correctly the health effects due to Chaetomium inhaled mycotoxins {87, 800}.

Infections and colonisations

Cases of confirmed human Chaetomium infection are rare. Chaetomium are among the fungi causing infections often referred to as phaeohyphomycosis or hyalohyphomycosis. Brain abscess, peritonitis, cutaneous and subcutaneous lesions may develop. Onychomycosis of the toenails or fingernails may be exceptionally caused by Chaetomium sp. in people with normal immunity {1760}.

The full spectrum of Chaetomium mycoses includes onychomycosis, sinusitis, empyema, pneumonia and fatal disseminated cerebral disease in immunocompromised hosts and intravenous drug users.

Several reports have been published, implicating species of Chaetomium as opportunistic infectious pathogens; in a case review, C. globosum was the most common species being isolated in, at least, nine clinical cases of infection {1755}. As the diagnosis of pulmonary fungal infections is difficult, in absence of a cultural isolate, some cases may have been falsely attributed to Aspergillus, both on clinical symptoms and even on histopathology exams {1743}.

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Respiratory infections have been reported. A first case of a pneumonia caused by C. globosum was reported in a patient with acute myeloblastic leukemia {740}. An other case was reported in a person with a history of asthma and chronic bronchiectasis, who developed a right-middle-lobe syndrome in his lung, following infection with a new strain, C. perlucidum {737}.

A case of pneumonia caused by Chaetomium globosum was diagnosed in a leukemic patient: the computed tomography chest scan revealed cavitating lesions characteristic of an invasive fungal infection in the right upper lobe, and a right lobectomy was performed. Histology demonstrated branching hyphae invading blood vessels that were “consistent with Aspergillus. This case was however confirmed by PCR as being caused by C. globosum {1743}.

Chaetomium was isolated from the bronchoalveolar lavage of an hospitalized patient nursed in a room where three patients colonised with this fungus had been housed before; the air filter system was subsequently found to be contaminated with Chaetomium {740}.

A paranasal sinuses infection, diagnosed in a women, revealed necrotic material with hyphae of Aspergillus fumigatus and perithecia of Chaetomium sp.; authors report that growth of Chaetomium can be stimulated in the presence of A. fumigatus {1754, 1753}.

Cerebral infections have been reported in patients presenting different risk factors. Three cases of fatal cerebral mycosis caused by C. strumarium have been reported in males with prior histories of intravenous drug use. These infections were most likely acquired by direct intravenous injection of the fungus and it’s subsequent spread; it was suggested that brain tissue provides an environment for rapid growth and proliferation of this fungus {741}.

A case of fatal invasive mycosis {737} has been reported in a patient with acute myelogenous leukemia: this infection was caused by a new species, C. perlucidum {737}. Chaetomium atrobrunneum, a new pathogen, has also been associated with cerebral infections in the immunocompromised hosts {1749}.

Cutaneous and subcutaneous phaeohyphomycosis were reported in people with non clinical signs of immunodeficiency {728, 1766}. Although onychomycosis is recognized to be caused by Chaetomium, there have been only few credible descriptions of this infection caused by this fungal genus {1736}. This onychomycosis can be successfully treated with itraconazole {729}.

Virulence factors

No particular virulence factors have been reported.

More details

However, when pathologic changes (consolidated lung lesions and histologic lesions) were studied following tracheal inoculation of goats, C. globosum seems to be the most infectious of the Chaetomium, ranking third of the seven fungi; C. globosum ranked third after Mucor ramosissmus and Trichoderma viride {902}.

Specific settings

Nosocomial infections

Very few Chaetomium spp. infections have been reported as possibly acquired in the hospital setting.

The genus Chaetomium is mentioned as part of the possible causative agents of nosocomial mycoses among the emerging fungal pathogens posing a risk for immunocompromised patients {1747, 2123}. However, events involving Chaetomium are hardly ever reported.

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In one instance, four bone marrow transplant recipients, who consecutively occupying the same room in an Oncology-Haematology Special Care Unit (OHSCU), became colonised with Chaetomium. Environmental cultures revealed Chaetomium contamination of the OHSCU air handling system, including the HEPA (high-efficiency particulate air) filters {1765}. At the time of Chaetomium colonisation, all patients were febrile, two had transient new infiltrates on chest X-rays, and three were receiving amphotericin B therapy.

Receiving antimicrobial agents or chemotherapy, immunosuppression, organ transplantation, neutropenia and presence of indwelling intravascular catheter are known risk factors for fungal infections and could be factors permitting Chaetomium infections in the hospital setting and during the peri-hospitalization period {1735}. Some of them can be a cause of devastating complications following fungal infections {740}. However, Chaetomium present in the hospital environment have been reported only in four occasions and only in immunocompromised subjects {740}.

Invasive and life-threatening Chaetomium infections have occurred in association with drug use (through direct inoculation), but the majority have involved patients with haematologic malignancy {1770} or immunosuppression secondary to a bone marrow transplantation (organ transplantation), a condition which appeared to be the most frequent risk factor {737, 1734, 1750, 1751, 1765}.

Occupational diseases

Type III hypersensitivity pneumonitides due to Chaetomium spp. are not known in any particular occupational settings. (See adverse health reactions section.)

Species of Chaetomium being clearly allergenic and growing readily in decaying plant material and compost, this fungus could represent a risk for workers exposed to such contaminated material.

Diagnostic tools

Cultures

No specific report of the diagnostic value of cultures or their success in cases of deep sited infections. (See laboratory section for possible culture results.)

Histopathology

The histological presentation of a deep-sited infection due to Chaetomium is typically that of an opportunistic fungal hyphal infection.

Immunochemical staining of lung sections from a pneumonia case, involving Chaetomium globosum, revealed branching hyphae in the tissue sections (see figure 1) {740}. Molecular confirmation of this invasive infection, by DNA amplification, has been obtained {1743}.

In one case of fatal cerebral mycosis, the section of brain, stained with Gomori methenamine-silver, showed branched septate hyphae, often with slight swellings (see figure 2). Many hyphae had grown around the blood vessels. The section from the deep white matter showed necrosis and dense acute inflammation and was positive for fungal elements by hematoxylin and eosin staining. A Masson-Fontana stain was only faintly positive. Acid-fast bacillus and Gram stain were negative {3317}.

Immunodiagnosis

Test IgE IgG Antigens Other
Skin Tests X      
RAST-IgE X      
RAST-IgG   X    
ELISA-ELIFA        
Immunodiffusion        
Immunofluorescence   Experimental    
Complement fixation        
PCR     Experimental  
Other        

More details

Les préparations d’allergènes les plus communes pour l’usage in vivo ou in vitro, qui sont disponibles sur le marché, sont le Chaetomium globosum et un « pool » d’espèces de Chaetomium {581, 3284}.

Les allergènes de Chaetomium répertoriés par la FDA sont les suivants :

GJ34 - Chaetomium globosum GJ35 - Chaetomium indicum GJ36 - Chaetomium olivaceum GJ37 - Chaetomium sp.

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July-28-16