Strategic Project - UI 690 - 2011-2012

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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.

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; 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.

2012Journal article

Restricted access

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.

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; 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

Propensity for biofilm formation by clinical isolates from urinary tract infections: developing a multifactorial predictive model to improve antibiotherapy

Publication . Alves, Maria José; Barreira, João C. M.; Carvalho, Inês; Trinta, Luis; Pereira, Liliana; Ferreira, Isabel C. F. R.; Pintado, Manuela

A group of biofilm-producing bacteria isolated from patients with urinary tract infections was evaluated, identifying the main factors contributing to biofilm formation. Among the 156 isolates, 58 (37.2 %) were biofilm producers. The bacterial species (P,0.001), together with patient’s gender (P50.022), were the factors with the highest influence for biofilm production. There was also a strong correlation of catheterization with biofilm formation, despite being less significant (P50.070) than species or gender. In fact, some of the bacteria isolated were biofilm producers in all cases. With regard to resistance profile among bacterial isolates, b-lactam antibiotics presented the highest number of cases/percentages – ampicillin (32/55.2 %), cephalothin (30/ 51.7 %), amoxicillin/clavulanic acid (22/37.9 %) – although the carbapenem group still represented a good therapeutic option (2/3.4 %). Quinolones (nucleic acid synthesis inhibitors) also showed high resistance percentages. Furthermore, biofilm production clearly increases bacterial resistance. Almost half of the biofilm-producing bacteria showed resistance against at least three different groups of antibiotics. Bacterial resistance is often associated with catheterization. Accordingly, intrinsic (age and gender) and extrinsic (hospital unit, bacterial isolate and catheterization) factors were used to build a predictive model, by evaluating the contribution of each factor to biofilm production. In this way, it is possible to anticipate biofilm occurrence immediately after bacterial identification, allowing selection of a more effective antibiotic (among the susceptibility options suggested by the antibiogram) against biofilm-producing bacteria. This approach reduces the putative bacterial resistance during treatment, and the consequent need to adjust antibiotherapy

2014Journal article

Open access