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PubMed1995

Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839.

Ten triprenyl phenol metabolites were isolated as inhibitors of pancreatic cholesterol esterase from cultures of Stachybotrys sp. F-1839 by solvent extraction and column chromatographies. Combination of spectroscopic analyses revealed that two of these compounds are K-76 (1) and stachybotrydial (2), and that the remaining eight are new congeners (designated F1839-A (3), -B (4), -C (5), -D (6), -E (7), -F (8), -I (9) and -J (10). These compounds inhibited pancreatic cholesterol esterase by 50% at 6 x 10(-5) to 1.1 x 10(-1) M. Inhibition of the enzyme by compound 2, the most potent one among these compounds, was time-dependent and irreversible. When administered to normal rats, 2, at a single oral dose of 100 mg/kg, reduced [14C]cholesterol absorption by 50-60%. In cholesterol-fed mice, dietary supplementation of 2 (0.1%) for 14 days resulted in a 20% reduction in serum total cholesterol level without causing significant change in the high density lipoprotein cholesterol level.

Animals↗
PubMed1996

Novel spirodihydrobenzofuranlactams as antagonists of endothelin and as inhibitors of HIV-1 protease produced by Stachybotrys Sp. I. Fermentation, isolation and biological activity.

Six novel spirodihydrobenzofuranlactams I - VI (1 - 6) and a related spirodihydrobenzofuranalcohol, the previously described natural compound L-671,776 (7), were isolated from cultures of two different Stachybotrys species. These secondary metabolites showed antagonistic effects in the endothelin receptor binding assay and inhibited HIV-1 protease. Both biological activities are novel for L-671,776 (7). The pseudosymmetric spirodihydrobenzofuranlactam VI (6) is the most potent representative of this class of compounds exhibiting IC50 values of 1.5 microM in the ET-A receptor binding assay and 11 microM in the HIV-1 protease inhibition assay.

Animals↗
PubMed1996

Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.

Animals↗
PubMed2001

Selective production of staplabin and SMTPs in cultures of Stachybotrys microspora fed with precursor amines.

Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys microspora, enhance fibrinolysis by modulating plasminogen conformation to increase its susceptibility to activation by plasminogen activators. We found that the production of these metabolites were markedly elevated by feeding the microbial culture with an amino acid or an amino alcohol that is a partial molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid, 2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45-fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8, respectively. Although the feeding at day 0 to 3 of culture supported the selective production, the supplementation after 5 days had little or no effect. When non-constituent amino acids were supplemented to cultures, production of hitherto uncharacterized congeners was observed.

Amino Acids↗
PubMedDate not supplied

The role of Stachybotrys mycotoxins in building-related illness.

Recently there has been increased attention among both the public and health professionals regarding the potential role of mycotoxins, primarily from fungi of the genus Stachybotrys, as etiologic agents related to illness among persons exposed in the indoor (nonindustrial) environment. Recommendations for the remediation of buildings are being made based in part on reported health effects believed to be due to mycotoxins. A search of NIOSHTIC (a literature database maintained by the National Institute for Occupational Safety and Health) and MEDLINE (from 1965 to present) for literature related to fungi, mycotoxins, and the indoor environment was conducted. References from relevant articles also were reviewed. This strategy yielded a total of 13 articles. Important issues concerning exposure assessment and case definitions are inadequately addressed in the literature reviewed, making it difficult to implicate mycotoxins as a cause of building-related illness. The literature review indicates that currently there is inadequate evidence supporting a causal relationship between symptoms or illness among building occupants and exposure to mycotoxins. Research involving the identification and isolation of specific fungal toxins in the environment and in humans is needed before a more definitive link between health outcomes and mycotoxins can be made.

Air Pollution, Indoor↗
PubMedDate not supplied

Stachybotrys chartarum (chartarum = atra = alternans) and other problems caused by allergenic fungi.

Stachybotrys chartarum is a cellulose-decaying fungus with worldwide distribution. It grows well at room temperature and with humidity above 93%. S. chatarum requires special media high in cellulose and low in sugar and nitrogen to compete with Penicillium and Aspergillus. Ninety percent of field-collected spores are not culturable. S. chartarum can produce macrocyclic trichothecenes but is highly dependent on strain and environmental conditions. In strains implicated in mycotoxicosis, not all produce detectable trichothecenes. Therefore, the presence of S. chartarum is not proof of toxin presence. Trichothecenes are potent inhibitors of protein and DNA synthesis. By the inhalation route, occupational stachybotrytoxicosis causes chest and upper airway symptoms, fever, leucopenia, dermatitis; starts in 2-3 days of exposure; and lasts 3 weeks. Investigation of the environment of the cluster of pulmonary hemorrhage in 10 infants in Cleveland, Ohio, and similar cases elsewhere are presented. The Centers for Disease Control and Prevention considers S. chartarum a serious health threat. However, even though there are now techniques of measuring S. chartarum conidia and estimating trichothecene mycotoxin in indoor air samples, no standards exist that relate to health effects. Those standards available are numerical or comparison of indoor/outdoor counts or both. Upper limit of noncontaminated indoor environment is 100-1000 colony-forming units (CFU) m3. There is no compelling evidence that exposures expected in most mold-contaminated indoor environments are likely to result in measurable health effects. However, when the health care worker suspects a problem in the home environment, a questionnaire and home visit may be helpful. High indoor exposures are associated with infrequent ventilation or vacuuming, pets, visible mold, and old carpets. To screen the indoor air, an experienced pollen and mold counter could use a Burkard personal air sampler. Health-based exposure standards for molds and mycotoxins do not exist. When available data indicate extremely high mold levels, cleanup consisting of removal of all contaminated material, cleaning accessible heating, ventilation, and airconditioning parts and filters, and preventive maintenance are indicated. There is a brief summary of the diseases of plants, animals, and humans caused by several common allergenic fungi and the mycotoxins they produce.

Air Microbiology↗
PubMedDate not supplied

[A comparative analysis of Stachybotrys chartarum strains isolated in Russia].

This work deals with a comparative analysis of Stachybotrys chartarum strains isolated from various artificial cellulose-containing materials and natural substrates in the geographically distant regions of Russia. The analysis included the determination of the spore size, the strain toxicity to Paramecium caudatum, the strain resistance to the fungicides Benomil, Olilen, and Tilt, and the PCR study of the genome structure with the aid of a primer that was complementary to the core sequence of the SINE retrotransposon. It was found that some of the strains that were isolated from different areas and from different substrates differ in their toxicity, fungicide resistance, and genome structure. The PCR analysis showed the absence of any correlation between the genome structure, the strain properties, the geographic area, and the substrates from which the strains were isolated. The pheno- and genotypic diversity of the strains and their different vegetative compatibility suggest the existence of an intraspecies diversity of the S. chartarum strains that were isolated in different geographic areas. The absence of any correlation between the pheno- and genotypic properties of the strains and the substrates from which they were isolated implies that the colonization of artificial substrates by S. chartarum occurred occasionally from natural habitats. The S. chartarum populations that live on artificial substrates are unlikely to have their own evolutionary history.

Animals↗
PubMed2005

[Wall relative humidity: a simple and reliable index for predicting Stachybotrys chartarum infestation in dwellings].

As the indoor mold Stachybotrys chartarum (SC) has been linked to serious health disorders, its identification in water-damaged dwellings is of utmost importance. The aim of this work was to compare wall relative humidity (RH) measurements with the results of mold identification studied on 458 samples collected from 100 dwellings. Mold identification was based on direct microscopic examination of wall samples collected by the gummed paper technique. Mean (+/- SD) wall RH (%) was much higher (97.0 +/- 6.1) when SC was identified (30 samples) than when other molds were identified (291 samples, 41.8 +/- 36.9) and when no molds were identified (137 samples, 38.9 +/- 34.8). There was a direct relationship between wall and room-air RH but the scatter of results implies that the latter cannot be used as a surrogate for the former. This study suggests that simple wall RH measurement can serve as a reliable indicator of SC infestation of dwellings.

Air Pollution, Indoor↗
PubMed2006

Pulmonary cytotoxicity of secondary metabolites of Stachybotrys chartarum (Ehrenb.) Hughes.

Damp dwellings represent suitable conditions for extended indoor moulds. A cellulolytic micromycete Stachybotrys chartarum (Ehrenb.) Hughes is considered to be a tertiary colonizer of surfaces in affected buildings. Known adverse health effects of S. chartarum result from its toxins--trichothecenes or atranones, as well as spirolactams. Mechanism of their potential pathological effects on the respiratory tract has not yet been sufficiently clarified. The cytotoxic effects of complex chloroform-extractable endo- (in biomass) and exometabolites (in cultivation medium) of an indoor S. chartarum isolate of an atranone chemotype, grown on a liquid medium with yeast extract and sucrose at 25 degrees C for 14 d, on lung tissue were evaluated in the 3-day experiment. For the purpose, 4 mg of toxicants were intratracheally instilled in 200 g Wistar male rats. A trichothecene mycotoxin diacetoxyscirpenol was used as the positive control. Bronchoalveolar lavage (BAL) parameters--viability and phagocytic activity of alveolar macrophages (AM), activity of lactate dehydrogenase, acid phosphatase and cathepsin D in cell-free BAL fluid (BALF), as well as in BAL cells, were measured. Acute exposure to the metabolites caused statistically significant changes, indicating lung tissue injury in the experimental animals. Decreased AM viability and increased activity of lysosomal enzyme cathepsin D in BAL cells after fungal exometabolite exposure were the most impressive. As toxic principles were found predominantly in the growth medium, toxins were more likely responsible for lung cell damage than e.g. fungal cell wall components. S. chartarum toxic metabolites can contribute to the ill health of occupants of mouldy building after inhalation of contaminated aerosol.

Animals↗
PubMed1982

Some cultural conditions that control production of verrucarin J, a cytotoxic metabolite of Stachybotrys chartarum.

A suitable chemically defined culture medium was selected and some optimal conditions for the biosynthesis of the highly cytostatic and antifungal compound verrucarin J were reported. Medium of the following composition was favourable for the production of verrucarin J by Stachybotrys chartarum: sucrose, 50; NaNO3, 2.0; KH2PO4, 1.0; MgSO4, 0.5; KCl, 0.5; leucine, 1.0 and FeSO4, 0.01 (g/l of distilled water). Biosynthesis of verrucarin J was maximal (11.8 mg/l) at pH 6.5-7.0 and after incubation for 14 days at 25 degrees C.

Antibiotics, Antineoplastic↗
PubMed1997

Effects of intranasal exposure to spores of Stachybotrys atra in mice.

The effects of highly toxic and nontoxic spores of Stachybotrys atra were investigated in mice after six intranasal administrations of 1 x 10(5) and 1 x 10(3) spores in phosphate-buffered saline during a 3-week period. Toxic spores contained the trichothecene mycotoxins, satratoxins G and H, as well as the immunosuppressant stachybotrylactones and -lactams. No trichothecenes were detected in the nontoxic spores, and they contained only minor amounts of stachybotrylactones and -lactams. In mice injected with toxic and nontoxic spores, the platelet count was decreased and leucocyte and erythrocyte counts, hemoglobin concentration, and hematocrit were increased. No IgG antibodies to S. atra were detected in sera of mice exposed intranasally to spores. No histological changes were detected in spleen, thymus, or intestines of mice. The mice receiving 1 x 10(5) toxic spores intranasally developed severe inflammatory changes within both bronchioles and alveoli. Hemorrhage was detected in alveoli. The mice receiving 1 x 10(5) nontoxic spores also developed inflammatory changes in the lungs, but these changes were significantly milder than those in mice receiving toxic spores. The mice receiving 1 x 10(3) toxic spores developed inflammatory changes in the lungs that were less severe than those in the mice receiving 1 x 10(5) toxic spores. No inflammatory changes were detected in the mice receiving 1 x 10(3) of nontoxic spores. The present findings indicate that exposure to S. atra spores containing toxins (satratoxins) can be a significant health risk.

Administration, Intranasal↗
PubMed1997

[Mass development of Stachybotrys chartarum on compostable plant pots made from recycled paper].

After handling plants grown in decomposable pots made of recycling paper, three women working in a big horticulture developed very painful inflammated efflorescences at the finger-tips, followed by scaling off the skin. The pots appeared to be very mouldy. Black masses of conidia of Stachybotrys chartarum and perithecia of Chaetomium globosum were identified on almost every pot. Apart from various other fungal genera, Trichoderma und Acremonium were frequently detected. Considering the observed symptoms, special attention was payed to the mycotoxin producing species St. chartarum. To evaluate the inhalative spore load, air sampling was performed. The detection of St. chartarum in the air was only possible with the spore trap (sampling of particles) but not with the Andersen sampler (detection of colony forming units). Without moving the pots, measurements yielded values of 30-100 St. chartarum conidia per m3 of air. The concentration of air-borne conidia increased drastically by handling the pots, thus attaining up to 7,500 conidia per m3 of air for St. chartarum only. The occurrence of St. chartarum in such amounts is alarming because of possible toxin production. In addition, the allergenic stress by fungal spores has to be emphasized. The results are discussed with regard to general medical-mycological aspects related to the degradation of environmentally-friendly decomposable materials.

Acremonium↗
PubMedDate not supplied

[The physiological and biochemical characteristics of Stachybotrys chartarum 13959a in relation to the biosynthesis of stachybotryotoxins].

The activities of key enzymes of main metabolic pathways: glycolysis, pentose phosphate pathway and tricarboxylic acid cycle, have been studied in dynamics of cultivation of toxin-producing fungus Stachybotrys chartarum 13959a. Aldolase activity increased while that of succinate dehydrogenase decreased during the fungal growth. The activity of glucose-6-phosphate dehydrogenase was high during the first days of cultivation and then it decreased. The maximum yield of acetaldehyde has been observed during the first stages of cultivation and it has not been connected with quantitative yield of pyruvate.

Acetaldehyde↗
PubMed1998

Effects of Stachybotrys chartarum (atra) conidia and isolated toxin on lung surfactant production and homeostasis.

This study evaluated the effects of Stachybotrys chartarum conidia and a trichothecene, isosatratoxin-F, on choline incorporation into DSPC by fetal rabbit alveolar type II cells and on alveolar surfactant subtypes in mice. Exposure of fetal rabbit type II cells to S. chartarum conidia at concentrations of 10(3) to 10(6) conidia ml(-1) significantly depressed [3H] choline incorporation after 24 h of exposure. Exposure of the rabbit cells to 10(5) to 10(6) conidia ml(-1) also resulted in significantly depressed [3H] choline uptake after 48 h. Additionally, fetal rabbit alveolar type II cells exposed to isosatratoxin-F in concentrations ranging from 10(-9) to 10(-4) M showed a significant reduction in [3H] choline incorporation into DSPC. Alveolar surfactant phospholipid concentrations in the different metabolic subfractions of lung lavage fluid of mice intratracheally exposed to either 50 microl of 10(7) ml(-1) S. chartarum conidia or 50 microl 10(-7) M isosatratoxin-F showed some significant changes at 12, 24, 48, and 72 h post-exposure, compared to the surfactant subfractions of control mice which were either untreated, exposed to saline or to 50 microl of 10(-7) ml(-1) Cladosporium cladosporioides conidia. In both the S. chartarum- and the isosatratoxin-F-treated mice, exposure significantly increased P10, P100, and S100 phospholipid concentrations, while the P60 phospholipid concentrations were depressed. In contrast, C. cladosporioides-treated mice showed only one significant change in subfraction phospholipid concentration: P60 was depressed at 48 h post-exposure. These results reveal that alveolar type II cells are sensitive to exposure to S. chartarum conidia and to isosatratoxin F. Sensitivity is manifest by alterations in the normal metabolic processing of alveolar surfactant. In exposed mice, this effect appears to involve a significant increase in newly secreted surfactant and an accumulation of the used surfactant forms.

Analysis of Variance↗
PubMed1980

A complement inhibitor produced by Stachybotrys complementi, nov. sp. K-76, a new species of fungi imperfecti.

A complement inhibitor, K-76, was isolated and purified from the culture supernatant of a fungus, Stachybotrys complementi, nov. sp. K-76, isolated from soil of Ishigaki Island, Okinawa. K-76 is a sesquiterpene compound and it can be oxidized to a monocarboxylic derivative (K-76 COOH), the sodium salt of which is very soluble and much less toxic than K-76. K-76 and K-76 COOH both inhibited complement activation by either the classical or alternative pathway. They inhibited generation of the factor chemotactic to human polymorphonuclear leukocytes from human serum by aggregated immunoglobulin. When sensitized erythrocytes were treated with complement in the presence of K-76 COOH, the resulting unlysed cells were found to be in the state of EACl, 4b, 2a, 3b. Thus K-76 COOH is considered to block mainly the C5 intermediate step. K-76 COOH did not inhibit any proteases or esterases tested, except when tested at high concentration.

Chemotactic Factors↗
PubMed1994

Production of Chitinases and beta-1,3-Glucanases by Stachybotrys elegans, a Mycoparasite of Rhizoctonia solani.

The in vitro production of chitinases and beta-1,3-glucanases by Stachybotrys elegans, a mycoparasite of Rhizoctonia solani, was examined under various culture conditions, such as carbon and nitrogen sources, pH, and incubation period. Production of both enzymes was influenced by the carbon source incorporated into the medium and was stimulated by acidic pH and NaNO(3). The activity of both enzymes was very low in culture filtrates from cells grown on glucose and sucrose compared with that detected on chitin (for chitinases) and cell wall fragments (for beta-1,3-glucanases). Protein electrophoresis revealed that, depending on the carbon source used, different isoforms of chitinases and beta-1,3-glucanases were detected. S. elegans culture filtrates, possessing beta-1,3-glucanase and chitinase activities, were capable of degrading R. solani mycelium.

Journal Article↗
PubMed1994

Stachybotrys atra Growth and Toxin Production in Some Building Materials and Fodder under Different Relative Humidities.

Growth of Stachybotrys atra and its toxin production on some building materials and in animal fodder were studied at relative humidities ranging from 78 to 100%. Toxins were detected by biological assays and chemical methods. Strong growth of the fungus and presence of macrocyclic trichothecenes, mainly satratoxins G and H, were detected on wallpaper and gypsum boards and in hay and straw at saturation conditions. On pine panels, S. atra grew well, but neither biological toxicity nor production of macrocyclic trichothecenes was observed.

Journal Article↗
PubMed2002

Stachyflin and acetylstachyflin, novel anti-influenza A virus substances, produced by Stachybotrys sp. RF-7260. I. Isolation, structure elucidation and biological activities.

Two novel compounds, stachyflin and acetylstachyflin, have been isolated by solid-state fermentation of Stachybotrys sp. RF-7260. The structures of both metabolites, determined by detailed NMR analyses and X-ray crystallographic analysis, are novel with a pentacyclic moiety including cis-fused decalin. The absolute stereochemistry of stachyflins was determined by circular dichroism analysis. Stachyflin showed antiviral activity against influenza A virus (H1N1) in vitro with an IC50 value of 0.003 microM. Acetylstachyflin was about 77-fold less active than stachyflin.

Antiviral Agents↗