Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. Because of their pharmacological activity, some mycotoxins or mycotoxin derivatives have found use as antibiotics, growth promotants, and other kinds of drugs; still others have been implicated as chemical warfare agents.
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Mycoses & Mycotoxicoses
Fungi are major plant and insect pathogens, but they are not nearly as important as agents of disease in vertebrates, i.e., the number of medically important fungi is relatively low. Frank growth of fungi on animal hosts produces the diseases collectively called mycoses, while dietary, respiratory, dermal, and other exposures to toxic fungal metabolites produce the diseases collectively called mycotoxicoses.
Mycoses range from merely annoying (e.g., athlete’s foot) to life-threatening (e.g., invasive aspergillosis). The fungi that cause mycoses can be divided into two categories, primary pathogens (e.g., Coccidioides immitis and Histoplasma capsulatum) and opportunistic pathogens (e.g., Aspergillus fumigatus and Candida albicans). Primary pathogens affect otherwise healthy individuals with normal immune systems. Opportunistic pathogens produce illness by taking advantage of debilitated or immunocompromised hosts. The majority of human mycoses are caused by opportunistic fungi (149, 172, 245, 265). The mechanisms of pathogenesis of both primary and opportunistic fungi are complex, and medical mycologists have devoted considerable research energy trying to identify the factors that distinguish fungal pathogens from saprophytic and commensal species (31, 66). Some infections remain localized, while others progress to systemic infection. For many mycoses, the ordinary portal of entry is through the pulmonary tract, but direct inoculation through skin contact is not uncommon.
In contrast to mycoses, mycotoxicoses are examples of “poisoning by natural means” and thus are analogous to the pathologies caused by exposure to pesticides or heavy metal residues. The symptoms of a mycotoxicosis depend on the type of mycotoxin; the amount and duration of the exposure; the age, health, and sex of the exposed individual; and many poorly understood synergistic effects involving genetics, dietary status, and interactions with other toxic insults. Thus, the severity of mycotoxin poisoning can be compounded by factors such as vitamin deficiency, caloric deprivation, alcohol abuse, and infectious disease status. In turn, mycotoxicoses can heighten vulnerability to microbial diseases, worsen the effects of malnutrition, and interact synergistically with other toxins.
The number of people affected by mycoses and mycotoxicoses is unknown. Although the total number affected is believed to be smaller than the number afflicted with bacterial, protozoan, and viral infections, fungal diseases are nevertheless a serious international health problem. Mycoses caused by opportunistic pathogens are largely diseases of the developed world, usually occurring in patients whose immune systems have been compromised by advanced medical treatment. Mycotoxicoses, in contrast, are more common in underdeveloped nations. One of the characteristics shared by mycoses and mycotoxicoses is that neither category of illness is generally communicable from person to person.
Mycoses are frequently acquired via inhalation of spores from an environmental reservoir or by unusual growth of a commensal species that is normally resident on human skin or the gastrointestinal tract. These commensal species become pathogenic in the presence of antibacterial, chemotherapeutic, or immunosuppressant drugs, human immunodeficiency virus infection, in-dwelling catheters, and other predisposing factors (31, 66). The majority of mycotoxicoses, on the other hand, result from eating contaminated foods. Skin contact with mold-infested substrates and inhalation of spore-borne toxins are also important sources of exposure. Except for supportive therapy (e.g., diet, hydration), there are almost no treatments for mycotoxin exposure, although Fink-Gremmels (80) described a few methods for veterinary management of mycotoxicoses, and there is some evidence that some strains of Lactobacilluseffectively bind dietary mycotoxins (72, 73). Oltipraz, a drug originally used to treat schistosomiasis, has been tested in Chinese populations environmentally exposed to aflatoxin (111).
In plant pathology, many secondary metabolites produced by bacteria and fungi are pathogenicity or virulence factors, i.e., they play a role in causing or exacerbating the plant disease. The phytotoxins made by fungal pathogens of Cochliobolus (Helminthosporium) and Alternaria, for example, have well-established roles in disease development (287), and several mycotoxins made by Fusarium species are important in plant pathogenesis (62). On the other hand, there is relatively little evidence that mycotoxins enhance the ability of fungi to grow in vertebrate hosts. Aspergillus fumigatus is case in point. It is the major species associated with aspergillosis and produces gliotoxins (inhibitors of T-cell activation and proliferation as well as macrophage phagocytosis). However, gliotoxin is not known to be produced in significant amounts by Aspergillus fumigatus during human disease (265). On the other hand, there are reports that gliotoxin has been associated with infections by Candida albicans (230, 231). The ability to grow at human body temperature (37°C) is clearly an important requirement for systemic mycotic infection, but the optimum temperature for the biosynthesis of most mycotoxins is within a more mesophilic range (20 to 30°C). For this and other reasons, the current view is that while some mycotoxins are known pathogenicity factors in plants, their significance in human mycoses is not yet clear.
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