Strategic Project - LA 16 - 2011-2012

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Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies

Publication . Alves, Maria José; Ferreira, Isabel C.F.R.; Froufe, Hugo J.C.; Abreu, Rui M.V.; Martins, Anabela; Pintado, Manuela

Aim and Methods: Although the antimicrobial activity of extracts from several mushroom species have 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 in the mechanism of action of potential antimicrobial drugs for resistant microorganisms. 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 sensible Staphylococcus aureus. MRSA was inhibited by 2,4-dihydroxybenzoic, vanillic, syringic (MICs=0.5 mg/mL) and p-coumaric (MIC= 1 mg/mL) acids, while these compounds at the same concentrations had no inhibitory effects against methicillin sensible Staphylococcus aureus. Conclusions: The presence of carboxylic acid (COOH), two hydroxyl (OH) groups in para and ortho positions of the benzene ring, as 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 microorganisms resistant to commercial antibiotics.

2013Journal article

Open access

Docking studies in target proteins involved in mechanisms of antibacterial action: extending the knowledge on standard antibiotics to mushrooms antimicrobial 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.

2014Journal article

Open access

Wild mushroom extracts potentiate the action of standard antibiotics against multiresistant bacteria

Publication . Alves, Maria José; Ferreira, Isabel C.F.R.; Lourenço, Inês; Castro, Ana; Pereira, Liliana; Martins, Anabela; Pintado, Manuela

The main objective of the present work 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 multi-resistant microorganisms (Escherichia coli, Extended-spectrum beta-lactamase-producing (ESBL) Escherichia 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 multi-resistant bacteria. Significance and Impact of the Study: Mushroom extracts could decrease therapeutic doses of standard antibiotics and reduce microorganism’s resistance to those drugs.

2014Journal article

Open access

Wild mushroom extracts as inhibitors of bacterial biofilm formation

Publication . Alves, Maria José; Ferreira, Isabel C.F.R.; Lourenço, Inês; Costa, Eduardo Manuel; Martins, Anabela; Pintado, Manuela

Microorganisms can colonize a wide variety of medical devices, putting patients in risk for local and systemic infectious complications, including local-site infections, catheter-related bloodstream infections, and endocarditis. These microorganisms are able to grow adhered to almost every surface, forming architecturally complex communities termed biofilms. The use of natural products has been extremely successful in the discovery of new medicine, and mushrooms could be a source of natural antimicrobials. The present study reports the capacity of wild mushroom extracts to inhibit in vitro biofilm formation by multi-resistant bacteria. Four Gram-negative bacteria biofilm producers (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Acinetobacter baumannii) isolated from urine were used to verify the activity of Russula delica, Fistulina hepatica, Mycena rosea, Leucopaxilus giganteus, and Lepista nuda extracts. The results obtained showed that all tested mushroom extracts presented some extent of inhibition of biofilm production. Pseudomonas aeruginosa was the microorganism with the highest capacity of biofilm production, being also the most susceptible to the extracts inhibition capacity (equal or higher than 50%). Among the five tested extracts against E. coli, Leucopaxillus giganteus (47.8%) and Mycenas rosea (44.8%) presented the highest inhibition of biofilm formation. The extracts exhibiting the highest inhibitory effect upon P. mirabilis biofilm formation were Sarcodon imbricatus (45.4%) and Russula delica (53.1%). Acinetobacter baumannii was the microorganism with the lowest susceptibility to mushroom extracts inhibitory effect on biofilm production (highest inhibition—almost 29%, by Russula delica extract). This is a pioneer study since, as far as we know, there are no reports on the inhibition of biofilm production by the studied mushroom extracts and in particular against multi-resistant clinical isolates; nevertheless, other studies are required to elucidate the mechanism of action.

2014Journal article

Open access

A review on antimicrobial activity of mushroom (Basidiomycetes) extracts and isolated compounds

Publication . Alves, Maria José; Ferreira, Isabel C.F.R.; Dias, Joana F.; 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 multi-resistant 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 as source of new antimicrobials. In this review we present an overview about the antimicrobial properties of mushroom extracts, 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 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 highest antimicrobial activity against Gram-positive bacteria, while 2-aminoquinoline, isolated from Leucopaxillus albissimus, presents the highest antimicrobial activity against Gram-negative bacteria.

2012Journal article

Restricted access