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Institute for Bioengineering and Biosciences
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A CBM-Hexapeptide Fusion Confers Antimicrobial Properties to Cellulose

A CBM-Hexapeptide Fusion Confers Antimicrobial Properties to Cellulose | iBB | Scoop.it

A new strategy to modify cellulose with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) is proposed by BERG and BSIRG researchers that uses fusions of Cys-terminated derivatives of MP196 and a carbohydrate binding module (CBM). CBM3-MP196-modified cellulose hydrogels displayed antibacterial activity that was significantly higher when compared with controls. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. the paper was published in Acta Biomaterialia. The work was funded by project CBM-X.

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The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death

The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death | iBB | Scoop.it

The bacterial protein azurin shows an unexpected therapeutic effect against various types of cancer. This property seems to result from its unique structural and surface features. A 28-residue peptide (named p28) derived from the middle part of azurin has been subjected to various studies and reached two clinical trials phase I in US. In a recent paper published in Biomedicines, a iBB team (Ana Rita Garizo, Lígia Coelho, Sandra Pinto, Tiago Dias, Fábio Fernandes, Nuno Bernardes and Arsénio M Fialho) were able to identified another anticancer bioactive peptide (CT-p19LC) derived from the C-terminal of azurin. CT-p19LC proved to interact preferentially with cancer cells, causing a significative inhibition of cell proliferation in a dose dependent manner. Moreover, it is proposed that the mode of action of CT-p19LC involves perturbation or disruption of cancer cell membranes. Overall this study highlights the relevance of azurin as a source of bioactive peptides with potential application in cancer therapies.

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Phenotypic Characterization of Trimeric Autotransporter Adhesin-defective bcaC Mutant of Burkholderia cenocepacia

Phenotypic Characterization of Trimeric Autotransporter Adhesin-defective bcaC Mutant of Burkholderia cenocepacia | iBB | Scoop.it

The role of the bcaC  trimeric autotransporter adhesion (TAA) gene in the virulence of Burkholderia cenocepacia has been disclosed by iBB researchers Andreia Pimenta, Dalila Mil-Homens, Sandra Pinto and Arsénio Fialho in a report published in Microbes and Infection. TAAs are homotrimeric proteins of the outer membrane of many Gram-negative pathogens that play a key role in adhesion to host cells. Two insertional-mutants for TAA bcaC and histidine kinase (HK) BCAM0218 genes were constructed. Findings indicate that bcaC encodes for a large multifunctional TAA that has hemagglutination activity and is also required for maximal host cell adherence. The neighbor BCAM0218 HK encoding gene was identified as a critical player that negatively controls the expression of the bcaC TAA gene. All together, the findings represent a step forward for a better characterization of the subset of B. cenocepacia TAA-encoding genes. This article was selected as the highlighted article of the July 2020 issue of the Microbes and Infection journal.

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Antagonist Biocompatibility of Zn-based Materials Functionalized with Metal Oxides

Antagonist Biocompatibility of Zn-based Materials Functionalized with Metal Oxides | iBB | Scoop.it

Zinc surfaces coated with nanostructured ZnO flowers has received increasing attention as a versatile biomaterial for medical applications. A collaborative work between researchers from CQE (Marta Alves, Catarina Santos and Fátima Montemor) and iBB (Dalila Mil-Homens, Sandra Pinto) describes the successful functionalization of these surfaces with cooper (Cu), iron (Fe) or manganese (Mn) oxides (Ox). The in vitro study of  these surfaces,  by fibroblast viability,  hemocompatibility, and  chick  chorioallantoic membrane (CAM) assays revealed the potential brought by CuOx functionalization for anti-cancer applications, with the antagonist behaviour of the surfaces functionalized with MnOx, and in a less extent with FeOx, favouring wound healing in traumatic  processes. Despite the possible correlation between biocompatibility and   hydroxyapatite   precipitation,   no   correlation   could   be   drawn with the corrosion activity, study by immersion and electrochemical techniques, of these surfaces. The study resulted from. The results were published in Colloids and Surfaces B: Biointerfaces.

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Azurin Perturbs Lipid Rafts’ Organization and Enhances Sensitivity to Anti-cancer Drugs

Azurin Perturbs Lipid Rafts’ Organization and Enhances Sensitivity to Anti-cancer Drugs | iBB | Scoop.it

A new determinant of the interaction of the bacterial anti-cancer protein azurin with the lipid rafts present in the membrane of cancer cells has been uncovered by a team led by Arsénio Fialho from BSRG-iBB, in collaboration with Sandra Pinto and Fábio Fernandes from CQFM-IN and iBB. The lipid rafts in these cells contribute to increase membrane order, rigidity and resistance to anti-cancer drugs. As a consequence of the interaction with lipid rafts, we demonstrate that treating cells with azurin increases membrane fluidity, and ultimately benefits the action of other drugs, probably by facilitating its entry in cancer cells. The work was recently published in the journal Cell Cycle.

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The Stress-response Protein BolA Influences Fitness and Promotes Salmonella Typhimurium Virulence

The Stress-response Protein BolA Influences Fitness and Promotes Salmonella Typhimurium Virulence | iBB | Scoop.it
BolA is an important  regulatory protein that is responsible for bacterial survival in late stages of growth and under harsh environmental conditions. In a recent publication in Applied Enviromental Microbiology, researchers from BSRG-iBB (Dalila Mil-Homens, Sandra Pinto and Arsénio M. Fialho), in collaboration with the group of Cecília Arraiano from ITQB NOVA, attempt to unveil the role played by BolA protein in Salmonella pathogenesis. Specifically, the authors describe the use of an in vitro and in vivo non-mammalian model of infection (larval hemocytes and the larvae of the greater wax moth Galleria mellonella) to dissect several aspects of virulence associated with the virulence determinant BolA from Salmonella Typhimurium. The work constitutes a relevant step towards the comprehension of BolA protein and may have an important impact for future studies in other organisms. Click on title to learn more.
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Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement

Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement | iBB | Scoop.it

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial to many cellular processes in eukaryotes, including membrane trafficking, signal transduction, ion channel function  and cytoskeleton dynamics. This function multiplicity is partially achieved through a dynamic spatiotemporal organization of PI(4,5)P2 within the membrane. In a recent paper published in IJMS, an IBB team (Maria J. Sarmento, Luís Borges-Araújo, Sandra N.Pinto, Nuno Bernardes, Joana Ricardo, Ana Coutinho, Manuel Prieto and Fábio Fernandes) was able to quantify PI(4,5)P2 confinement in living cells making use of FRET imaging measurements. PI(4,5)P2 was found to be significantly compartmentalized at the plasma membrane of HeLa cells. These PI(4,5)P2 enriched domains were shown to not depend on cholesterol content, ruling out an association with lipid rafts. On the other hand, upon inhibition of actin polymerization, compartmentalization of PI(4,5)P2 was almost entirely eliminated, confirming that the cytoskeleton network is the critical component responsible for the formation of nanoscale PI(4,5)P2 domains.

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Half-Sandwich Cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype

Half-Sandwich Cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype | iBB | Scoop.it

The effectiveness of antiplasmodial drugs against the blood stage of infection is increasingly threatened by the emergence and spread of drug-resistant parasites. Here a small library of “half-sandwich” cyclopentadienylruthenium(II) compounds of the general formula [(η5-C5R5)Ru(PPh3)(N-N)][PF6] was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2, and artemisinin-resistant IPC5202 Plasmodium falciparum strains and the liver stage of Plasmodium berghei. We showed that some of the compounds are potent dual-stage antiplasmodials, displaying Plasmodium falciparum-selective accumulation in infected erythrocytes. The study was coordinated by researchers from Faculdade de Farmácia with collaboration of researchers from IHMT, IMM and iBB-IST (Sandra Pinto). The results were published in Inorg. Chem. 

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New Hybrids of Graphene Quantum Dots and Glycol Corroles for Multiphoton Bioimaging

New Hybrids of Graphene Quantum Dots and Glycol Corroles for Multiphoton Bioimaging | iBB | Scoop.it

Graphene quantum dots (GQDs) possess excellent optical properties, high photostability, aqueous solubility and bio-compatibility. In this work, we report for the first time a two-step methodology for the efficient covalent functionalization of GQDs with corrole macrocycles. The resulting hybrids were explored as imaging agents and thus their internalization and distribution in live animal cells was evaluated in cancer cell lines (MCF-7, human breast adenocarcinoma cell line) using confocal laser scanning microscopy. The study was coordinated by researchers from CQE-IST (Ermelinda Maçoas) and University of Aveiro (Carla Santos) and also with collaboration of researchers from Complutense University of Madrid and iBB-IST (Sandra Pinto). The results were published in Carbon.

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Sandra Pinto Delivers Oral Presentation at the 29th ECCMID

Sandra Pinto Delivers Oral Presentation at the 29th ECCMID | iBB | Scoop.it

Sandra Pinto from BSIRG-IBB delivered an oral presentation at the 29th European Congress of Clinical Microbiology & Infectious Diseases titled “Optimisation of confocal microscopy imaging techniques to study the diffusion-controlled action of a cationic antimicrobial peptide along Staphylococcus biofilms”. In this work the biofilm mass, metabolic activity and viability were quantified using conventional techniques, while fluorescence imaging methods, including a real-time calcein-release assay, were employed to investigate the kinetics of pepR activity at different biofilm depths. The authors showed that pepR has limited diffusion and activity on the inner layers of a staphylococcal biofilm, and results are consistent with almost irreversible binding of the peptide to the biofilm matrix. The work involves a collaboration between researchers from BSIRG-iBB, BSRG-iBB, IMM and Universitat Pompeu Fabra. The conference took place in Amsterdam, Holland, on the 13-16th April.

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Yeast Response to Acetic Acid Involves Pdr18-mediated Ergosterol Transport at the Membrane

Yeast Response to Acetic Acid Involves Pdr18-mediated Ergosterol Transport at the Membrane | iBB | Scoop.it

The ability of Saccharomyces cerevisiae to overcome the stress induced by cytotoxic compounds depends on the activity of plasma membrane transporters of the ABC superfamily, presumably through the questionable unspecific efflux of multiple drugs and xenobiotic compounds. A recent paper by iBB researchers provides new insights into the biological role of the ABC transporter of the pleiotropic drug resistance family of putative drug efflux pumps Pdr18, proposed to mediate ergosterol incorporation in plasma membrane. Pdr18 expression was found to help cells to counteract acetic acid-induced decrease of plasma membrane lipid order, increase the non-specific membrane permeability and decrease the transmembrane electrochemical potential. Results support the notion that Pdr18-mediated multistress resistance is linked to the status of plasma membrane lipid environment related with ergosterol content and the associated plasma membrane properties. The paper, published in Scientific Reports, results from the PhD project of Cláudia Godinho, advised by Prof. Isabel Sá-Correia from BSRG-iBB in collaboration with Fábio Fernandes and Sandra Pinto from BSIRG-iBB).

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