Solomon P. Wasser

Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides

Abstract. The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of polysaccharides with antitumor and immunostimulating properties. Many, if not all, Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, culture broth. Data on mushroom polysaccharides have been collected from 651 species and 7 infraspecific taxa from 182 genera of higher Hetero- and Homobasidiomycetes. These polysaccharides are of different chemical composition, with most belonging to the group of β-glucans; these have β-(1→3) linkages in the main chain of the glucan and additional β-(1→6) branch points that are needed for their antitumor action. High molecular weight glucans appear to be more effective than those of low molecular weight. Chemical modification is often carried out to improve the antitumor activity of polysaccharides and their clinical qualities (mostly water solubility). The main procedures used for chemical improvement are: Smith degradation (oxydo-reducto-hydrolysis), formolysis, and carboxymethylation. Most of the clinical evidence for antitumor activity comes from the commercial polysaccharides lentinan, PSK (krestin), and schizophyllan, but polysaccharides of some other promising medicinal mushroom species also show good results. Their activity is especially beneficial in clinics when used in conjunction with chemotherapy. Mushroom polysaccharides prevent oncogenesis, show direct antitumor activity against various allogeneic and syngeneic tumors, and prevent tumor metastasis. Polysaccharides from mushrooms do not attack cancer cells directly, but produce their antitumor effects by activating different immune responses in the host. The antitumor action of polysaccharides requires an intact T-cell component; their activity is mediated through a thymus-dependent immune mechanism. Practical application is dependent not only on biological properties, but also on biotechnological availability. The present review analyzes the pecularities of polysaccharides derived from fruiting bodies and cultured mycelium (the two main methods of biotechnological production today) in selected examples of medicinal mushrooms.

Medicinal mushroom modulators of molecular targets as cancer therapeutics

Empirical approaches to discover anticancer drugs and cancer treatments have made limited progress in the past several decades in finding a cure for cancer. The expanded knowledge of the molecular basis of tumorigenesis and metastasis, together with the inherently vast structural diversity of natural compounds found in mushrooms, provided unique opportunities for discovering new drugs that rationally target the abnormal molecular and biochemical signals leading to cancer. This review focuses on mushroom low-molecular-weight secondary metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell cycle regulation, and signal transduction cascades. Also discussed in this review are high-molecular-weight polysaccharides or polysaccharide–protein complexes from mushrooms that appear to enhance innate and cell-mediated immune responses, exhibit antitumor activities in animals and humans, and demonstrate the anticancer properties of selenium compounds accumulated in mushrooms.

Current findings, future trends, and unsolved problems in studies of medicinal mushrooms

The target of the present review is to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the twenty-first century. Special attention is paid to mushroom polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and cultured broth. The data on mushroom polysaccharides are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. The chemical structure of polysaccharides and its connection to antitumor activity, including possible ways of chemical modification, experimental testing and clinical use of antitumor or immunostimulating polysaccharides, and possible mechanisms of their biological action, are discussed. Numerous bioactive polysaccharides or polysaccharide–protein complexes from medicinal mushrooms are described that appear to enhance innate and cell-mediated immune responses and exhibit antitumor activities in animals and humans. Stimulation of host immune defense systems by bioactive polymers from medicinal mushrooms has significant effects on the maturation, differentiation, and proliferation of many kinds of immune cells in the host. Many of these mushroom polymers were reported previously to have immunotherapeutic properties by facilitating growth inhibition and destruction of tumor cells. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom polymers appears central. Particularly and most importantly for modern medicine are polysaccharides with antitumor and immunostimulating properties. Several of the mushroom polysaccharide compounds have proceeded through phases I, II, and III clinical trials and are used extensively and successfully in Asia to treat various cancers and other diseases. A total of 126 medicinal functions are thought to be produced by medicinal mushrooms and fungi including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemia, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects.

Fungal life in the extremely hypersaline water of the Dead Sea: first records

The first report, to our knowledge, on the occurrence of filamentous fungi in the hypersaline (340 g salt l–1) Dead Sea is presented. Three species of filamentous fungi from surface water samples of the Dead Sea were isolated: Gymnascella marismortui (Ascomycota), which is described as a new species, Ulocladium chlamydosporum and Penicillium westlingii (Deuteromycota). G. marismortui and U. chlamydosporum grew on media containing up to 50% Dead Sea water. G. marismortui was found to be an obligate halophile growing optimally in the presence of 0.5 to 2 M NaCl or 10 to 30% (by volume) of Dead Sea water. Isolated cultures did not grow on agar media without salt, but grew on agar prepared with up to 50% Dead Sea water. This suggests that they may be adapted to life in the extremely stressful hypersaline Dead Sea.

Medicinal Mushroom Science: Current Perspectives, Advances, Evidences, and Challenges

The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

Carbon and nitrogen sources influence the ligninolytic enzyme activity of Trametes versicolor

Among carbon sources studied, cellobiose and mannitol provided the highest laccase (Lac) activity (648 and 742 U1-1, respectively) of Trametes versicolor 775 while glucose gave maximum manganese peroxidase (MnP) and peroxidase activities (44 and 114U1-1, respectively). Citrus fruit peel as growth substrate enhanced Lac activity 7-fold when compared to the medium with cellobiose, whereas grape vine sawdust increased MnP and peroxidase activity up to 148 and 677U1-1, respectively.

Spatiotemporal diversity of filamentous fungi in the hypersaline Dead Sea

To investigate the spatial and temporal diversity in the fungal community of the Dead Sea, we collected Dead Sea water samples at eight near-shore localities and at different stations offshore over a 1-year period (1999–2000). In addition, depth profiles were sampled at a deep station (304 m) in the centre of the sea. In the course of the study we obtained 476 isolates, comprising 38 species from 19 genera of Oomycota (1), Zygomycota (2), Ascomycota (13), and mitosporic fungi (3). This brings the total number of species recovered from the Dead Sea to 55. Approximately 43% of the isolates belonged to the genera Aspergillus and Eurotium . Most of the species found appeared only in winter. Fungal diversity increased near the outlets of less saline springs near the shore. The species Aspergillus terreus, A. sydowii, A. versicolor, Eurotium herbariorum, Penicillium westlingii, Cladosporium cladosporoides and C. sphaerospermum were isolated consistently and probably form a stable core of the community. The results suggest that a remarkably diverse fungal diversity may be found in the hypersaline Dead Sea waters. To what extent the fungal diversity recovered was present as dormant spores or as vegetative mycelia remains to be determined.

Evolutionary Theory and Processes: Modern Perspectives

The HLA system, which was discovered by virtue of the fact that it was polymorphic, shows an extraordinary extent of polymorphism making it an attractive candidate for human population studies. The variation in the number of alleles at different loci, together with the pattern of variation within a gene in relation to its function, provides clear evidence for the role of natural selection in maintaining the polymorphism. Some specifities such as HLA-A*02 are remarkable in the extent to which they have minor variants with different frequencies in different parts of the world. The HLA polymorphism is old and the sequences tbat tend to be conserved are epitopes which may occur in different combinations in different alleles. Close linkage between these loci generates a considerable level of linkage disequilihrium so that haplotype frequencies tum out to be very valuable for the characterisation of populations and their interrelationships. HLA distribution data have made major contributions, for example, to theories of the migration of early farmers across Europe. The selective basis for the generation and maintenance of the HLA polymorphism almost certainly lies in the importance of immune response differences for resistance to infection. A modern consequence is the association of particular HLA types with a variety of autoimmune diseases. The HLA system was discovered by virtue of the fact that it was polymorphic. The impetus for its discovery was the search for genetic differences to match for transplantation, by analogy with the human red cell blood groups. The serological reagents used for the initial description of the antigens on human white blood cells came from multiply transfused individuals and later from multiparous women. These antibodies were produced because of the existence of polymorphic differences between individuals which were necessarily at the level of proteins expressed on the cell surface. Since essentially all the genes relevant to the HLA system have now been cloned, and following the development of a wide variety of approaches for polymorphism detection at the DNA level, virtually all characterisation of the HLA polymorphism can now be done using DNA-based methods. The extent of HLA polymorphism, apparent even from the earliest investigations, made it an obvious and attractive candidate for human population

Survival of filamentous fungi in hypersaline Dead Sea water

A variety of filamentous fungi have recently been isolated from the Dead Sea (340 g/L total dissolved salts). To assess the extent to which such fungi can survive for prolonged periods in Dead Sea water, we examined the survival of both spores and mycelia in undiluted Dead Sea water and in Dead Sea water diluted to different degrees with distilled water. Mycelia of Aspergillus versicolor and Chaetomium globosum strains isolated from the Dead Sea remained viable for up to 8 weeks in undiluted Dead Sea water. Four Dead Sea isolates (A. versicolor, Eurotium herbariorum, Gymnascella marismortui, and C. globosum) retained their viability in Dead Sea water diluted to 80% during the 12 weeks of the experiment. Mycelia of all species survived for the full term of the experiment in Dead Sea water diluted to 50% and 10% of its original salinity. Comparison of the survival of Dead Sea species and closely related isolates obtained from other locations showed prolonged viability of the strains obtained from the Dead Sea. Spores of isolates obtained from the terrestrial shore of the Dead Sea generally proved less tolerant to suspension in undiluted Dead Sea water than spores of species isolated from the water column. Spores of the species isolated from the control sites had lost their viability in undiluted Dead Sea water within 12 weeks. However, with the exception of Emericella spores, which showed poor survival, a substantial fraction of the spores of Dead Sea fungal isolates remained viable for that period. The difference in survival rate between spores and mycelia of isolates of the same species points to the existence of adapted halotolerant and/or halophilic fungi in the Dead Sea.

Ecological stress and sex evolution in soil microfungi

The elucidation of the origin and maintenance of sex is a major unsolved problem in evolutionary biology. A number of hypotheses have been elaborated, but the scarcity of empirical data limits further progress. During recent years, the general inclination has changed towards pluralistic models of sex evolution, due partly to an increased diversity of studied organisms. Fungi are among the most promising organisms for testing sexual causation, as demonstrated in recent laboratory experiments. However, reconciling theory and evidence necessitates critical field observations. Here, we report new estimates of the distribution of morphologically sexual and asexual soil microfungi in nature, which indicate a remarkable trend towards increased sexuality with increasing climatic stress.