Fungal toxins as a parasitic factor responsible for the establishment of fungal infections

Although the mechanism of fungal infections, particularly that of opportunistic fungus infections, has been studied extensively, much still remains to be clarified. As is the case for certain bacterial infections, it has long been assumed by numerous investigators that some toxins, enzymes and other metabolites produced in vitro as well as in vivo by pathogenic fungi or their cellular constituents might be responsible for the establishment of fungal infections. However, there are very few papers which deal with isolation and/or characterization of pathogenic fungus-derived toxins, particularly those of high molecular weight, to sufficiently meet various criteria for toxins including etiopathological ability. Likewise, it has been speculated that certain enzymes produced by pathogenic fungi are related to the pathogenesis of infections with the fungi implicated, but no direct evidence has been provided.It is commonly held by researchers concerned with medical mycology that the lowering of specific and/or nonspecific resistance of a host to pathogenic fungi is a prerequisite for the establishment of infections, particularly opportunistic infections. However, it is also accepted that if a given fungus possesses no parasite factors (e.g. toxigenicity, invasiveness and others), it would be unable to initiate infection even when the host is in a severe immunodeficient state. This is supported by our recent studies working with Saccharomyces cerevisiae and some other so-called nonpathogenic yeasts (unpublished data). Based on these considerations, the author and his co-workers have attempted to isolate several high and low molecular weight toxins in a pure state from virulent strains of Candida albicans and Aspergillus fumigatus as opportunist. Studies have also been made on the etiopathological roles of some successfully isolated toxins in infections with the fungi implicated (46).In addition to our experimental results, general concepts in fungal toxins, particularly those related to such toxins as isolated in our laboratory are outlined. Since opportunistic fungus infections have created a global problem because of their world-wide prevalence, a sharp demarcation between the so-called pathogenic and nonpathogenic fungi has become vague. Despite this situation, two terms are conventionally used throughout this paper.The author thanks Drs. H. Yamaguchi and K. Uchida, Y. Yamamoto, T. Hiratani, and Y. Nozu for their collaboration during these studies.