Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building–Related Illness: New Insights into a Public Health Enigma

Abstract

TOXICOLOGICAL SCIENCES 104(1), 4–26 (2008) doi:10.1093/toxsci/kfm284 Advance Access publication November 15, 2007 REVIEW Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building–Related Illness: New Insights into a Public Health Enigma James J. Pestka,*,†,‡,1 Iwona Yike,§ Dorr G. Dearborn,§ Marsha D. W. Ward,{ and Jack R. Harkema*,k *Center for Integrative Toxicology; †Department of Microbiology and Molecular Genetics; ‡Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824; §Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, Ohio 44106; {U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711; and kDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824 Received September 26, 2007; accepted November 9, 2007 Damp building–related illnesses (DBRI) include a myriad of respiratory, immunologic, and neurologic symptoms that are sometimes etiologically linked to aberrant indoor growth of the toxic black mold, Stachybotrys chartarum. Although supportive evidence for such linkages is limited, there are exciting new findings about this enigmatic organism relative to its environ- mental dissemination, novel bioactive components, unique cellular targets, and molecular mechanisms of action which provide insight into the S. chartarum’s potential to evoke allergic sen- sitization, inflammation, and cytotoxicity in the upper and lower respiratory tracts. Macrocyclic trichothecene mycotoxins, pro- duced by one chemotype of this fungus, are potent translational inhibitors and stress kinase activators that appear to be a critical underlying cause for a number of adverse effects. Notably, these toxins form covalent protein adducts in vitro and in vivo and, furthermore, cause neurotoxicity and inflammation in the nose and brain of the mouse. A second S. chartarum chemotype has recently been shown to produce a