Mycotoxins and Other Biologically Active Metabolites
The mycotoxins and other biologically active compounds produced by S. chartarum are of concern to human health (23,32,33,57). Mycotoxin poisoning by this fungus is referred to as stachybotryotoxicosis.
S. chartarum produces a variety of macrocylic trichothecenes and related trichoverroids: roridin E and L-2; satratoxins F, G, and H; isosatratoxins F, G, and H; verrucarins B and J; and the trichoverroids, trichoverrols A and B and trichoverrins A and B. The satratoxins are generally produced in greater amounts than the other trichothecenes, but all compounds are produced in low quantities. They apparently occur in all parts of the fungus (53). The difficulty in obtaining, identifying, and purifying these toxins has slowed extensive studies on their biological activity. Hinkley and Jarvis (23) recently published analytical methods for the identification and quantification of bioactive compounds produced by this fungus. These methods were designed to quantitate individual compounds in culture extracts and detect low levels of trichothecenes in samples.
Macrocyclic trichothecenes are highly toxic compounds with a potent ability to inhibit protein synthesis (32). Numerous studies have demonstrated the toxicity of toxins from S. chartarum on animals and animal and human cells (42,45,49,51). Yang et al. (62) reported that satratoxin G was the most cytotoxic of eight trichothecenes tested on mammalian cells, even more toxic than the well known T-2 toxin associated with alimentary toxic aleukia. Other researchers have also reported the high toxicity of satratoxins compared to other trichothecenes (18). The LD50 in mice for satratoxins is ~1 mg/kg (32).
In addition, the fungus produces nine phenylspirodrimanes (spirolactones and spirolactams) and cyclosporin, which are potent immunosuppressive agents (33). Jarvis et al. (33) suggested that the combination of trichothecenes and these immunosuppressive agents may be responsible for the observed high toxicity of this fungus. New biologically active compounds are still being discovered in cultures of S. chartarum. Hinkley et al. (24,25) recently described the metabolites atranones A-G and two dolabellane diterpenes, but the complete biological activity of these compounds is unknown. Vesper and colleagues (57,59,60) reported some isolates produce Stachylysin, a hemolysin (compounds that lyse erythrocytes), and a hydroxamate siderophore. They suggest these compounds could be pathogenicity factors involved in pulmonary hemorrhage in infants exposed to S. chartarum.
There is considerable variation among isolates of S. chartarum in the production of mycotoxins and other metabolites (2,24,27,34,40). Indeed, Hinkley et al. (25) suggest there are two chemotypes of the fungus: the atranone and the macrocyclic trichothecene producers.
History of the Problem
In the Ukraine and other parts of eastern Europe during the 1930s, there were outbreaks of a new disease in horses and other animals that was characterized by symptoms such as irritation of the mouth, throat, and nose; shock; dermal necrosis; a decrease in leukocytes; hemorrhage; nervous disorder; and death (10,14,17,26,28). In 1938, Russian scientists determined the disease was associated with S. chartarum (then known as S. alternans) growing on the straw and grain fed to the animals. Intensive studies were then conducted resulting in the first demonstrated toxicity of S. chartarum in animals. Horses were actually fed cultures of the fungus. Contents from 30 petri plates containing the fungus were fed to horses and resulted in death, while even the contents of one plate resulted in sickness. Horses seem to be especially susceptible to these toxins; 1 mg of pure toxin is reported to cause death (14). Most outbreaks were associated with hay or feed that became infested during storage under wet conditions. The Russians coined the term stachybotryotoxicosis for this new disease. Since then, stachybotryotoxicosis has been reported on numerous farm animals from various parts of the world, especially in eastern Europe, but apparently has not been reported on animals in North America (26,55,61).
Hyperplastic dermatitis on a horse four days after feeding on straw infested with S. chartarum. Notice the scaly appearance of the upper lip area. Photograph reprinted from Sarkisov, A. Kh. 1954. Mikotoksikozi (Gribkovye otravleniia). Moscow. 216 pp. (click image for larger view).
Straw contaminated with S. chartarum (top) compared to clean straw. Persons handling this heavily contaminated straw could develop stachybotryotoxicosis.
In the late 1930s, stachybotryotoxicosis was reported in humans working on collective farms in Russia (10,14,17,29). People affected were those who handled hay or feed grain infested with S. chartarum or were exposed to the aerosols of dust and debris from the contaminated materials. Some of these individuals had burned the straw or even slept on straw-filled mattresses. The infested straw was often black from growth of the fungus.
