CYTOLYTIC TOXINS OF BASIDIOMYCETES

Abstract

Toxins with cytolytic action are widely distributed in the fungus realm. Five of them, proteins with direct haemolytic activity, have been isolated: Phallolysin [Seeger and co-workers, 1973] from Amanita phalloides, a thermo- and acid-labile, basic protein with a molecular weight of ca. 30 000 daltons, lyzes red cells of various species, bovine and sheep erythrocytes being rather resistant. Besides red cells, a large variety of mammalian cells, normal as well as transformed ones, are affected; however, no therapeutic antitumour effect was observed. The i.v. LD50 in rats is ca. 50μ/kg. Toxicity is mainly due to intravascular haemolysis; direct cardiotoxic effects may occur, too. - Volvatoxin (Lin and co-workers, 1973) from Volvariella volvacea, a thermolabile protein consisting of two non-identical subunits with molecular weights of 50 000 and 23 000 daltons, lyzes human erythrocytes and in laboratory animals exhibits cardiotoxic effects in vitro and in vivo. The i.p. LD50 in mice is 1.23 mg/kg. - Flammutoxin [Lin and co-workers, 1974] from Flammulima velutipes, a thermolabile, acid protein with an apparent molecular weight of 22 000 daltons, lyzes red cells from various species, sheep, goat and toad cells being resistant. Furthermore, local irritation, cardiotoxic effects, histamine release and damage of tumour cells are observed. The i.p. LD50 in mice is 2.45 mg/kg. - Rubescenslysin (Seeger, 1976) from Amanita rubescens, a thermolabile, acid protein with a molecular weight of ca. 35 000 daltons, lyzes red cells from various species, differences in susceptibility being slight. The i.v. LD50 in rats is 1.4 mg/kg, severe obstruction of airways and signs of haemolysis being present. It is considered to act as a detergent. - Pleurotolysin (Bernheimer and Avigad, 1979) from Pleurotus ostreatus, an acid polypeptide of unusual amino acid composition, seems to exist in the form of dimers of 25 000 daltons. In haemolysis, species differences are pronounced, sheep erythrocytes being most susceptible. It probably functions as a detergent and sphingomyelin is involved in its cytolytic action. - The cytolysins so far isolated from mushrooms are labile proteins; hence, these toxins are not likely to be involved in human mushroom poisoning. However, some of them might become useful tools in membrane solubilisation.