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Research Project
Portuguese Wild Mushrooms: Chemical characterization and functional study of antiproliferative and proapoptotic properties in cancer cell lines
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Wild mushroom extracts potentiate the action of standard antibiotics against multiresistant bacteria
Publication . Alves, Maria José; Ferreira, I.C.F.R.; Lourenço, I.; Castro, A.; Pereira, L.; Martins, A.; Pintado, M.
Aims: The main objective of this study was to evaluate the capacity of wild
mushroom extracts to potentiate the action of standard antibiotics, through
synergisms that allow a decrease in their therapeutic doses and ultimately
contribute to the reduction of resistances.
Methods and Results: Wild mushroom extracts were applied to different
multiresistant micro-organisms (Escherichia coli, extended-spectrum betalactamase-
producing (ESBL) E. coli and methicillin-resistant Staphylococcus
aureus (MRSA), combined with commercial antibiotics (penicillin, ampicillin,
amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, cotrimoxazol, levofloxacin).
Microdilution method was used to determine minimum inhibitory
concentrations (MICs). The results obtained showed higher synergistic effects
against MRSA than against E. coli. Mycena rosea and Fistulina hepatica were
the best extracts for synergistic effects against MRSA. The efficiency of Russula
delica extract against E. coli 1 (resistant to ampicillin, ciprofloxacin and
trimethoprim/sulfasoxazole) and E. coli 2 (resistant to amoxicillin/clavulanic
acid and ampicillin) was higher than that of Leucopaxillus giganteus extract;
nevertheless, the latter extract exhibited better synergistic effects against ESBL
E. coli.
Conclusions: This study shows that, similarly to plants, some mushroom
extracts can potentiate the action of antibiotics extensively used in clinical
practice for Gram-positive or Gram-negative bacteria, with positive action even
against multiresistant bacteria.
Significance and Impact of the Study: Mushroom extracts could decrease
therapeutic doses of standard antibiotics and reduce micro-organism’s
resistance to those drugs.
A review on antimicrobial activity of mushroom (basidiomycetes) extracts and isolated compounds
Publication . Alves, Maria José; Ferreira, Isabel C. F. R.; Dias, Joana; Teixeira, Vânia; Martins, Anabela; Pintado, Manuela
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 grampostive 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.
Docking studies in target proteins involved in antibacterial action mechanisms: Extending the knowledge on standard antibiotics to antimicrobial mushroom compounds
Publication . Alves, Maria José; Froufe, Hugo J. C.; Costa, Ana F. T.; Santos, Anabela F.; Oliveira, Liliana G.; Osório, Sara R. M.; Abreu, Rui M. V.; Pintado, Manuela; Ferreira, Isabel C. F. R.
In the present work, the knowledge on target proteins of standard antibiotics was
extended to antimicrobial mushroom compounds. Docking studies were performed for
34 compounds in order to evaluate their affinity to bacterial proteins that are known targets
for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis,
inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites.
After validation of the molecular docking approach, virtual screening of all the compounds
was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), D-alanyl-D-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase
subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate
reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom
compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism
of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets.
A review on antifungal activity of mushroom (basidiomycetes) extracts and isolated compounds
Publication . Alves, Maria José; Ferreira, Isabel C. F. R.; Dias, Joana; Teixeira, Vânia; Martins, Anabela; Pintado, Manuela
The present review reports the antifungal activity of mushroom extracts and isolated compounds including high (e. g. peptides and proteins) and low (e. g. sesquiterpenes and other terpenes, steroids, organic acids, acylcyclopentenediones and quinolines) molecular weight compounds. Most of the studies available on literature focused on screening of antifungal activity of mushroom extracts, rather than of isolated compounds. Data indicate that mushroom extracts are mainly tested against different Candida species, while mushroom compounds are mostly tested upon other fungi. Therefore, the potential of these compounds might be more useful in food industry than in clinics. Oudemansiella canarii and Agaricus bisporus methanolic extracts proved to be the most active mushroom extracts against Candida spp. Grifolin, isolated from Albatrellus dispansus, seemed to be the most active compound against phytopathogenic fungi. Further studies should be performed in order to better understand the mechanism of action of this and other antifungal compounds as well as safety issues.
Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies
Publication . Alves, M. J.; Ferreira, I. C. F. R.; Froufe, H. J. C.; Abreu, Rui M. V.; Martins, A.; Pintado, M.
Aim and Methods: Although the antimicrobial activity of extracts from several mushroom species has been reported, studies with the individual compounds present in that extracts are scarce. Herein, the antimicrobial activity of different phenolic compounds identified and quantified in mushroom species from all over the world was evaluated. Furthermore, a structure-activity relationship (SAR) analysis and molecular docking studies were performed, in order to provide insights into the mechanism of action of potential antimicrobial drugs for resistant micro-organisms. Results: 2,4-Dihydroxybenzoic and protocatechuic acids were the phenolic compounds with higher activity against the majority of Gram-negative and Gram-positive bacteria. Furthermore, phenolic compounds inhibited more MRSA than methicillin-susceptible Staphylococcus aureus. MRSA was inhibited by 2,4-dihydroxybenzoic, vanillic, syringic (MICs = 0.5 mg ml(-1)) and p-coumaric (MIC = 1 mg ml(-1)) acids, while these compounds at the same concentrations had no inhibitory effects against methicillin-susceptible Staph. aureus. Conclusions: The presence of carboxylic acid (COOH), two hydroxyl (OH) groups in para and ortho positions of the benzene ring and also a methoxyl (OCH3) group in the meta position seems to be important for anti-MRSA activity. Significance and Impact of the Study: Phenolic compounds could be used as antimicrobial agents, namely against some micro-organisms resistant to commercial antibiotics.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
5876-PPCDTI
Funding Award Number
PTDC/AGR-ALI/110062/2009