Ganoderma lucidum (Ling Zhi) is a basidiomycete white rot macrofungus which has been used extensively as "the mushroom of immortality" in China, Japan, Korea and other Asian countries for 2000 years. A great deal of work has been carried out on therapeutic potential of Ganoderma lucidum. The basidiocarp, mycelia and spores of Ganoderma lucidum contain approximately 400 different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins/peptides and trace elements which has been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumor, chemo and radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-androgenic, anti-angiogenic, anti-herpetic, antioxidative and radical-scavenging, anti-aging, hypoglycemic, estrogenic activity and anti-ulcer properties. Ganoderma lucidum has now become recognized as an alternative adjuvant in the treatment of leukemia, carcinoma, hepatitis and diabetes. The macrofungus is very rare in nature rather not sufficient for commercial exploitation for vital therapeutic emergencies, therefore, the cultivation on solid substrates, stationary liquid medium or by submerged cultivation has become an essential aspect to meet the driving force towards the increasing demands in the international market. Present review focuses on the pharmacological aspects, cultivation methods and bioactive metabolites playing a significant role in various therapeutic applications.

Ganoderma lucidum: a potent pharmacological macrofungus.

This review describes biologically active natural products isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basdiomycota (basidiomycetes), and they along with certain Ascomycota are a major source of pharmacologically active substances. There are about 25 000 species of basidiomycetes, of which about 500 are members of the Aphyllophorales, a polyphyletic group that contains the polypores. Many of these fungi have circumboreal distributions in North America, Europe, and Asia and broad distributions on all inhabited continents and Africa; only a small number of the most common species with the most obvious fruiting bodies (basidiocarps) have been evaluated for biological activity. An estimated 75% of polypore fungi that have been tested show strong antimicrobial activity, and these may constitute a good source for developing new antibiotics. Numerous compounds from these fungi also display antiviral, cytotoxic, and/or antineo...

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Biologically active compounds from Aphyllophorales (polypore) fungi.

Despite the huge diversity of antibacterial compounds, bacterial resistance to first-choice antibiotics has been drastically increasing. Moreover, the association between multiresistant microorganisms and nosocomial infections highlight the problem, and the urgent need for solutions. Natural resources have been exploited in the last years and among them, mushrooms could be an alternative source of new antimicrobials. In this review, we present an overview of the antimicrobial properties of mushroom extracts and highlight some of the active compounds identified, including low- and high-molecular weight (LMW and HMW, respectively) compounds. LMW compounds are mainly secondary metabolites, such as sesquiterpenes and other terpenes, steroids, anthraquinones, benzoic acid derivatives, and quinolines, but also primary metabolites such as oxalic acid. HMW compounds are mainly peptides and proteins. Data available from the literature indicate a higher antimicrobial activity of mushroom extracts against gram-positive bacteria. Among all the mushrooms, Lentinus edodes is the most studied species and seems to have a broad antimicrobial action against both gram-postive and gram-negative bacteria. Plectasin peptide, obtained from Pseudoplectania nigrella, is the isolated compound with the highest antimicrobial activity against gram-positive bacteria, while 2-aminoquinoline, isolated from Leucopaxillus albissimus, presents the highest antimicrobial activity against gram-negative bacteria.

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A Review on Antimicrobial Activity of Mushroom (Basidiomycetes) Extracts and Isolated Compounds

Beta-glucans from edible and medicinal mushrooms: Characteristics, physicochemical and biological activities

Aims: To evaluate the patterns of the production of antimicrobial compounds by diverse collection of actinomycetes isolated from different geographies under alternative conditions of pH and salinity in the media.



Methods and Results: Actinomycetes were grouped based on their method of isolation and their phenotype diversity was determined by total fatty acid analysis. A total of 335 representative isolates, including 235 Streptomyces species and 100 actinomycetes from other taxa, were screened for the production of antimicrobial activities against a panel of bacteria, filamentous fungi and yeasts, including some of clinical relevance. Production of antimicrobial activities was detected in 230 strains. In the case of the genus Streptomyces, 181 antimicrobial activities (77% of the tested isolates) were recorded. The activities observed among the other actinomycetes taxa were lower (49% of the tested isolates).



Conclusions: The results of this study support the idea that species of actinomycetes isolated in alternative selective conditions of pH and salinity present a significant capacity to produce compounds with antibacterial or antifungal activity. The best group of isolates in terms of production of active secondary metabolites was the one isolated in saline conditions.



Significance and Impact of the Study: The results demonstrate that these actinomycetes strains isolated in alternative selective conditions of pH and salinity and collected from diverse geographical locations present a significant capacity to produce compounds with antibacterial or antifungal activity.

https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2672.2003.02049.x

Patterns of antimicrobial activities from soil actinomycetes isolated under different conditions of pH and salinity.

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.

Screening of basidiomycetes for antimicrobial activities.

RESULTS Background: We have overcome the limitations of 40 years of ex vivo testing. The aim of this study is to determine the ability of Vivia's novel test (based on studying the ex-vivo sensitivity to drugs) to predict the complete remission (CR) rates after induction chemotherapy with cytarabine (Ara-C) and idarubicin (Ida) in 1st line AML.. Material and Methods: This has been an observational clinical trial where bone marrow samples from adult patients diagnosed with de novo AML in Spanish centers from the PETHEMA group were included. Whole marrow samples maintaining their Native Environment were incubated for 48h in well plates containing Ara-C, Ida, or their combination. Pharmacological responses are calculated using population models. Induction response was assessed according to the Cheson criteria (2003). Patients attaining a CR/CRi were classified as responders and the remaining as resistant. Results: 390 patient samples were used to calculate the dose response (DR) curves for Ara-C alone, Ida alone, and their synergism. For clinical correlation we used 142 patients with median 56 years. The strongest clinical predictors were the Area Under the Curve (AUC) of the DR of Ara-C (P=1.34E-05), and the AUC of IDA (P=3.9E-05). The GAM models revealed a significant relationship (RSquare=0.452 and deviance explained=45%) between these predictors and higher probabilities of post-induction resistance. Fig 1A shows a table illustrating the correlation between clinical outcome (columns) and the test predictions (lines). Using the cut off determined by the GAM models. The test obtain a high Specificity and Positive Protective Value (95% and 80,77%) and a lower sensitivity (50%) with a general prediction of a 81,69%. Interestingly, the 5 cases that the test identify as resistant but were clinically sensitive have high level of minimal residual disease. On the other hand, the test does not properly identify 21/142 that are clinically resistant and the test predicts as sensitive (bottom left quadrant right panel). This mismatched subgroup mimics the problems from molecular markers where a resistant clone present in a minority of leukemic cells cannot be detected yet drives the patient response. Consistent with this analysis, adding the cytogenetic risk factor to the ex vivo results, identifying the high risk population by molecular markers that might be present in a minority of the cells, significantly improves the correlation; Fig. 1B shows the 90% overall correlation achieved in 117 patient samples adding the cytogenetic risk factor, with a major improvement in the sensitivity from 50% to 72%. Both approaches lead to substantial improvements in estimated overall survival. ABSTRACT

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Pilar Hernandez

Papers

Screening of basidiomycetes for antimicrobial activities.

An ex vivo native environment precision medicine test shows high clinical correlation with responses to first line acute myeloid leukemia treatment

Development of a High-Throughput Screening Assay with Nurse-like Cell-Based Microenviroment in Chronic Lymphoid Leukemia Cells.