Chaetomium Species Research Articles

Implantation phaeohyphomycosis caused by a non-sporulating Chaetomium species

We report the case of a 66-year-old Iranian woman with a phaeohyphomycotic cyst (approximately 3×2.5cm in size) on the right lateral side of the neck. She had dysphagia and hoarseness, without any pain. She complained about discharge of black liquid on the skin and irritation. Histological examination of biopsy fragments from the lesions showed septate, branched brown hyphae. The fungus was cultured, but sporulation remained absent from 4- week-old cultures on Sabouraud dextrose agar (SDA), malt extract agar (MEA), potato dextrose agar (PDA), and water agar with sterile filter paper. Identification with the genus Chaetomium was achieved by sequencing the internal transcribed spacer (ITS) and the small subunit (SSU) domains of the rDNA gene and comparison with sequences held at GenBank and at the Centraalbureau voor Schimmelcultures (CBS). Sequencing of the SSU rRNA gene reveals this strain as belonging to the genus Chaetomium. The sequence of ITS did not fully match with any sequence of available ex-type strains of Chaetomium, Thielavia, Madurella and Papulaspora and hence might belong to an undescribed species. However, without diagnostic morphological features the taxon cannot be introduced as a novel member of the genus Chaetomium. After local excision of the cyst and antifungal therapy with ketoconazole (200mg twice a day), the lesion regressed and healed completely.

A new endophytic species of Chaetomium from Jatropha podagrica

A new endophytic species of Chaetomium from fruits of Jatropha podagrica is described from Maharashtra State, India. A combined sequence dataset of the ITS region, LSU rDNA, and β-tubulin genes supports recognition of this fungus as a new species that is largely concordant with morphological characters. Chaetomium jatrophae is characterized by spirally coiled, predominantly unbranched, and coarsely roughened terminal ascomatal hairs and elongate-ellipsoidal ascospores with a subapical or lateral germ pore. It is a mesophilic Chaetomium species with a temperature maximum of 40±0.2°C.

Targeted Disruption of Transcriptional Regulators inChaetomium globosumActivates Biosynthetic Pathways and Reveals Transcriptional Regulator-Like Behavior of Aureonitol

Postgenomic analysis revealed that many microorganisms carry numerous secondary metabolite biosynthetic genes on their genome. However, activities of those putative genes are not clearly reflected in the metabolic profile of the microorganisms, especially in fungi. A recent genome mining effort is promising in discovering new natural products. However, many fungi and other organisms are not amenable to molecular genetics manipulations, making the study difficult. Here we report successful engineering of Chaetomium globosum, a known producer of various valuable natural products, that allows its genetic manipulation via targeted homologous recombination. This strain permitted us to abolish transcriptional regulators associated with epigenetic silencing of secondary metabolite biosynthetic pathways, leading to the identification of the products generated by different gene clusters and isolation of novel secondary metabolites. We were able to identify six gene clusters that are responsible for the biosynthesis of 11 natural products previously known to be produced by C. globosum, including one cytochalasan and six azaphilone-type compounds. In addition, we isolated two new compounds, mollipilin A and B, that were only recently identified in a related Chaetomium species. Furthermore, our investigation into the mechanism of biosynthesis of those natural products in C. globosum also led to the discovery of a secondary metabolite, aureonitol, that acts like a transcriptional regulator for the biosynthesis of other secondary metabolites. Similar approaches should facilitate exploration of the untapped potential of fungal biosynthetic capability and identification of various unique biological functions that those secondary metabolites possess.

Method for Rapid Detection and Identification of Chaetomium and Evaluation of Resistance to Peracetic Acid

In the beverage industry, peracetic acid has been increasingly used as a disinfectant for the filling machinery and environment due to merits of leaving no residue, it is safe for humans, and its antiseptic effect against fungi and endospores of bacteria. Recently, Chaetomium globosum and Chaetomium funicola were reported resistant to peracetic acid; however, little is known concerning the detail of peracetic acid resistance. Therefore, we assessed the peracetic acid resistance of the species of Chaetomium and related genera under identical conditions and made a thorough observation of the microstructure of their ascospores by transmission electron microscopy. The results of analyses revealed that C. globosum and C. funicola showed the high resistance to peracetic acid (a 1-D antiseptic effect after 900 s and 3-D antiseptic effect after 900 s) and had thick cell walls of ascospores that can impede the action mechanism of peracetic acid. We also developed specific primers to detect the C. globosum clade and identify C. funicola by using PCR to amplify the β-tubulin gene. PCR with the primer sets designed for C. globosum (Chae 4F/4R) and C. funicola (Cfu 2F/2R) amplified PCR products specific for the C. globosum clade and C. funicola, respectively. PCR with these two primer sets did not detect other fungi involved in food spoilage and environmental contamination. This detection and identification method is rapid and simple, with extremely high specificity.

Phylogenetic Findings Suggest Possible New Habitat and Routes of Infection of Human Eumyctoma

Eumycetoma is a traumatic fungal infection in tropical and subtropical areas that may lead to severe disability. Madurella mycetomatis is one of the prevalent etiologic agents in arid Northeastern Africa. The source of infection has not been clarified. Subcutaneous inoculation from plant thorns has been hypothesized, but attempts to detect the fungus in relevant material have remained unsuccessful. The present study aims to find clues to reveal the natural habitat of Madurella species using a phylogenetic approach, i.e. by comparison of neighboring taxa with known ecology. Four species of Madurella were included in a large data set of species of Chaetomium, Chaetomidium, Thielavia, and Papulaspora (n = 128) using sequences of the universal fungal barcode gene rDNA ITS and the partial LSU gene sequence. Our study demonstrates that Madurella species are nested within the Chaetomiaceae, a family of fungi that mainly inhabit animal dung, enriched soil, and indoor environments. We hypothesize that cattle dung, ubiquitously present in rural East Africa, plays a significant role in the ecology of Madurella. If cow dung is an essential factor in inoculation by Madurella, preventative measures may involve the use of appropriate footwear in addition to restructuring of villages to reduce the frequency of contact with etiologic agents of mycetoma. On the other hand, the Chaetomiaceae possess a hidden clinical potential which needs to be explored.

An additional update on the genus Chaetomium with descriptions of two coprophilous species, new to Italy

Two Chaetomium species new to Italy, C. brasiliense and C. succineum, are described and an updated key to coprophilous Chaetomium from Italy is provided. All author’s collections of 23 species so far known from dung in Italy are listed. Following the recent publications describing new species, the worldwide key to Chaetomium species is updated.

The Novel Anti-Myeloma Agent Chaetocin Enhances Tumor-Specific Dendritic Cell Response Via the Induction of Heat Shock Protein and Cancer Testis Antigens On Myeloma Cells

AbstractAbstract 4066 Background:Dendritic cell (DC) based immunotherapy is emerging as a useful tool to treat multiple myeloma (MM). Although several tumor target antigens have been used, the clinical effectiveness of the vaccination is still limited. Chaetocin is a small molecule thiodioxopiperazine natural-product produced by Chaetomium species fungi currently in development as a candidate antimyeloma therapeutic, and has potent in vitro and in vivo activity conveyed by its ability to impose increased levels of cellular oxidative stress. Chaetocin has also been found to be used as histone methyl-transferase inhibitor with interest in the compound sufficient to kill various cancer cells. We investigated whether chaetocin could be used to induce apoptotic bodies for loading into DCs to enhance myeloma specific antitumor responses. Methods:Chaetocin was used to induce the apoptotic U266 myeloma cells, which were used as the sources of tumor antigens to loading onto DCs to generate myeloma-specific cytotoxic T lymphocytes (CTLs). Results:Chaetocin showed to induce apoptotic cells mostly from tumor cells and led to increase the expression of heat shock protein 90 (HSP90) at a level comparable to bortezomib. The transfer of activating signal from chaetocin-induced tumor cells to induce DCs maturation is mediated by the exposure of HSP90 on the surface of apoptotic cells. The HSP90 inhibitor geldanamycin can block this immunogenicity. Chaetocin up-regulate the expression of cancer testis antigens MAGEA3 and MAGEC1/CT7, which are commonly expressed in MM and the potent targets for active immunotherapies. The cytokines production during uptake tumor antigens and maturation was comparable in DCs loaded with either irradiated MM cells or chaetocin-induced MM cells. However, DCs loaded with chaetocin-induced MM cells can reduce the production of an inhibitory cytokine (IL-10) after stimulation with CD40 ligand. CTLs stimulated by chaetocin-induced MM cells-loaded DCs showed the increasing of CD8+T cells and displayed a greater number of IFN-g-secreting cells than did those stimulated by other DCs loaded with MM cell made by other conditions. Conclusion:These results indicate that anti-myeloma drug-induced apoptotic cells can be used as the source of myeloma antigens to loading onto DCs that could elicit potent anti-myeloma activity of CTLs due to the expression of heat shock proteins and cancer testis antigens as a mechanism of immunogenic death of human MM cells. Disclosures:No relevant conflicts of interest to declare.

Chaetoglobosins and azaphilones produced by Canadian strains of Chaetomium globosum isolated from the indoor environment

Chaetomium globosum is one of the most common species of fungi found growing on damp building materials in North America and Europe. At doses that could be experienced in a building with some mould damage, exposure to metabolites from other fungi results in inflammatory changes in vivo and in vitro. This research requires knowledge of the dominant toxins produced by fungal strains from the built environment and characterization of pure compounds for toxicity testing. We examined 25 strains of C. globosum isolated from the built environment in Canada. In varying amounts, these strains primarily produced chaetoglobosin A, C and F, chaetomugilin D, and chaetoviridin A. Spectroscopic data of the major isolated compounds are provided. Previous studies reported a number of metabolites from this species that we did not find. However, this appears to be due to misidentifications of the fungi they examined as well as problems with the analytical methods used. In addition, our data support the use of metabolite profiles for resolving the taxonomy of some economically important Chaetomium species.

ChemInform Abstract: Synthesis and Biological Activities of Chaetocin and Its Derivatives

AbstractReview: 34 refs.

Três espécies de Chaetomium (Chaetomiaceae – Ascomycota) da região semiárida do Brasil

During surveys for decomposer ascomycetes of plant debris, three previously described species of Chaetomium were collected: C. funicola, C. homopilatum and C. longicolleum. Descriptions, taxonomic comments, geographical distributions, and illustrations are presented for the species.

Synthesis and biological activities of chaetocin and its derivatives

Chaetocin, a natural product isolated from fungi of Chaetomium species, is a member of the epipolythiodiketopiperazines (ETPs), which have various biological activities, including cytostatic and anticancer activities. Recently, the inhibitory activity toward histone methyltransferases (HMTs) was discovered for chaetocin. We previously reported the first total synthesis of chaetocin and various derivatives. During studies on the structure–activity relationship for HMT inhibition, we found that the enantiomer of chaetocin (ent-chaetocin) is a more potent apoptosis inducer than natural chaetocin in human leukemia HL-60 cells. Mechanistic studies showed that ent-chaetocin induces apoptosis through the caspase-8/caspase-3 pathway.

The family Chaetomiaceae from China 4. Two newly recorded species of Chaetomium

Two species of the genus Chaetomium, C. virescens and C. senegalense, are reported as newly recorded species in China. The characteristics of the two species are described and illustrated from our materials. These specimens and living cultures examined were deposited in Herbarium of Fungi in Northwest A&F University (HMUABO).

Morphological, cultural, and biodestructive peculiarities of Chaetomium species

Chaetomium is a fungus species that inhabits different cellulose substrates. Some species of this genus destroy books, textile, and wood. This genus is of particular interest due to its antagonistic and enzyme peculiarities. Studies on morphological and cultural features of Chaetomium species have both theoretical and practical output. Growth rates and development of C. globosum, C. funicola, C. elatum, and C. spirale were studied under different temperatures (17–20°C, 25°C, 27°C, 30°C, and 33–35°C) and carbon source media (glucose, saccharose, mannite, lactose, amylum, and cellulose). The optimal growth temperature was 25–27°C for all the studied species, while the temperature range of 33–35°C inhibited the colonies’ growth. Growth dynamics and colony shape and morphology, as well as development of overhead mycelium and ascocarps, varied greatly in different Chaetomium species in regard to the carbon source media. When comparing the destructive effect of four studied species and C. murorum on craft paper, the highest activity was registered for C. globosum, C. funicola, and C. elatum.

The genus Chaetomium in Iran, a phylogenetic study including six new species

Twenty-one species of Chaetomium known from Iran were compared on the basis of morphological and molecular characters. Six new species are recognized, five isolated from cereals and one from nematode cysts. A combined sequence dataset of the ITS region, partial LSU rDNA, and β-tubulin gene sufficiently resolved five species groups of Chaetomium that are largely concordant with combined features of peridium structure, ascospore shape and germ pore position. Among the new species C. undulatulum is a close relative of C. globosum, C. rectangulare is close to C. elatum, C. interruptum and C. grande are close to C. megalocarpum, altogether forming the C. globosum species group. Chaetomium iranianum and C. truncatulum are members of the C. carinthiacum species group, characterized by spirally coiled ascomatal hairs and fusiform ascospores. A chrysosporium-like anamorph is newly described for C. acropullum.

Phaeohyphomycosis and onychomycosis due toChaetomiumspp., including the first report ofChaetomium brasilienseinfection

Chaetomium species have been rarely described as aetiological agents of invasive and dermatomycotic infections in humans. The majority of cases have been reported within the last two decades. Treatment failed in most of these cases. In this paper we present two cases in which Chaetomium spp. can be clearly identified as an aetiological agent in pathological conditions. In the first report, we describe a new aetiological agent, Chaetomium brasiliense, which was implicated in a case of otitis externa in a patient with spinocellular carcinoma basis cranii. The patient had been repeatedly treated for relapsing otitis externa and had previously undergone surgery several times for otitis media. The fungal aetiology was confirmed by repeated positive culture and histologic studies. The second case involved onychomycosis with strikingly brown nail discoloration due to Chaetomium globosum in an otherwise healthy patient. The nail lesion was successfully cured by oral terbinafine. The determination of both species was supported by sequencing of rDNA regions. The morphological aspect of Chaetomium spp. identification is also discussed. In vitro antifungal susceptibility tests demonstrated that both isolates were susceptible to terbinafine and azole derivates except fluconazole. Amphotericin B was effective only against the C. brasiliense strain. We review the literature to summarize clinical presentations, histologic findings, and treatment strategies.

Distribution of sterigmatocystin in filamentous fungi

During the last 50 y, the carcinogenic mycotoxin sterigmatocystin (ST) has been reported in several phylogenetically and phenotypically different genera: Aschersonia, Aspergillus, Bipolaris, Botryotrichum, Chaetomium, Emericella, Eurotium, Farrowia, Fusarium, Humicola, Moelleriella, Monocillium and Podospora. We have reexamined all available strains of the original producers, in addition to ex type and further strains of each species reported to produce ST and the biosynthetically derived aflatoxins. We also screened strains of all available species in Penicillium and Aspergillus for ST and aflatoxin. Six new ST producing fungi were discovered: Aspergillus asperescens, Aspergillus aureolatus, Aspergillus eburneocremeus, Aspergillus protuberus, Aspergillus tardus, and Penicillium inflatum and one new aflatoxin producer: Aspergillus togoensis (= Stilbothamnium togoense). ST was confirmed in 23 Emericella, four Aspergillus, five Chaetomium, one Botryotrichum and one Humicola species grown on a selection of secondary metabolite inducing media, and using multiple detection methods: HPLC–UV/Vis DAD, – HRMS and – MS/MS. The immediate precursor for aflatoxin, O-methylsterigmatocystin was found in Chaetomium cellulolyticum, Chaetomium longicolleum, Chaetomium malaysiense and Chaetomium virescens, but aflatoxin was not detected from any Chaetomium species. In all 55 species, representing more than 11 clades throughout the Pezizomycotina, can be reliably claimed to be ST producers and 13 of these can also produce aflatoxins. It is not known yet whether the ST/aflatoxin pathway has been developed independently 11 times, or is the result of partial horizontal gene transfer.

Fungal Assemblages in the Rhizosphere and Rhizoplane of Grasses of the Subfamily Panicoideae in the Lakkavalli Region of Karnataka, India

Fungal communities associated with roots play an important role in nutrient cycling, supporting plant growth and the biocontrol of plant diseases. Experiments were conducted in 2004-2006 to isolate and characterize, based on their morphological features, rhizosphere and rhizoplane fungi from perennial grasses of the subfamily Panicoideae growing in forests of the Western Ghats in India. Fungal species were isolated on potato dextrose, czapeck dox and water agar, in different locations and seasons. The results obtained on PDA were used for detailed analysis since most fungi occurred in high percentages. While certain grasses harbored diverse fungal species, others supported only a few species. Most fungi were isolated during winter followed by the rainy and summer seasons. The species richness, diversity and evenness of fungal assemblages in the rhizosphere and rhizoplane depended on the grass species and season. Ascomycetes were isolated in large numbers in most grass species. Species of Aspergillus, Chaetomium, Penicillium and Trichoderma occurred frequently. Certain others and non-sporulating fungi were grass species-specific. Most fungal species colonized the middle of the root more than the root tip or root base. Results suggest that perennial grasses harbor diverse fungal communities whose potential could be tapped for producing secondary metabolites and managing plant diseases.

Antihepatoma activity of chaetocin due to deregulated splicing of hypoxia-inducible factor 1α pre-mRNA in mice and in vitro

Chaetocin, an antibiotic produced by Chaetomium species fungi, was recently found to have antimyeloma activity. Here we examined whether chaetocin has anticancer activities against solid tumors. Chaetocin inhibited the growth of mouse and human hepatoma grafts in nude mice. Immunohistochemical analyses revealed that chaetocin inhibits hypoxia-inducible factor-1α (HIF-1α) expression and vessel formation in the tumors. Chaetocin also showed antiangiogenic anticancer activities in HIF-1α(+/+) fibrosarcoma grafted in mice, but not in HIF-1α(-/-) fibrosarcoma. Biochemical analyses showed that chaetocin down-regulated HIF-1α and the transcripts of HIF-1 target genes including vascular endothelial growth factor in hepatoma tissues and in various hepatoma cell lines. Based on the reported literature, unsuccessful efforts were made to determine the mechanism underlying the action of chaetocin. Unexpectedly, chaetocin was found to cause the accumulation of HIF-1α premessenger RNA (pre-mRNA) but to reduce mature mRNA levels in hepatoma cells and tissues. Such an effect of chaetocin was not observed in cell lines derived from normal cells, and was cell type-dependent even among cancer cell lines. Our results suggest that chaetocin could be developed as an anticancer agent to target HIF-1 in some cancers including hepatoma. It is also suggested that the HIF-1α pre-mRNA splicing is a novel therapeutic target for controlling HIF-1-mediated pathological processes.

The endophytic mycota associated with Vitis vinifera in central Spain

This study investigates the diversity of fungal endophytes associated with several varieties of grapevines with differing modes of cultivation in the Madrid region (central Spain). Our goal is to screen for and identify new fungal biocontrol agents against vine diseases, especially those associated with young plants produced in nurseries. A total of 500 fungal strains representing 68 taxa from six locations were isolated and characterised. Differences regarding cultivar and plant part processed were analysed in terms of composition and relative abundance of species. Some of the more frequently isolated strains represented were Acremonium, Alternaria, Aureobasidium, Botryotinia, Cladosporium, Epicoccum, Fusarium, Gibberella, Nectria, Penicillium, Phoma and Trichoderma species. Botryosphaeria species and Phomopsis viticola were also frequently isolated and may be vine pathogens. Several species of Acremonium, Phoma (P. glomerata) and Chaetomium showed promising antagonistic activity at the laboratory scale.

Unnatural enantiomer of chaetocin shows strong apoptosis-inducing activity through caspase-8/caspase-3 activation

Chaetocin, a natural product isolated from Chaetomium species fungi, was reported to have various biological activities, including antitumor and antifungal activities. Recently, we reported the first total synthesis of chaetocin and its derivatives. Here, we examined the cell-death-inducing activity of these compounds in human leukemia HL-60 cells. The unnatural enantiomer of chaetocin ( ent-chaetocin) was more potent than chaetocin, and was found to induce apoptosis through the caspase-8/caspase-3 activation pathway.