iBB

5-Flucytosine (5-FC) is an antifungal pro-drug whose use is limited due to the acquisition of 5-FC resistance by fungal pathogens. In this study, the response of the pathogenic yeast Candida glabrata to 5-FC was evaluated at the level of the membrane proteome. New aspects of the cell response to 5-FC were observed by BSRG researchers led by Miguel Teixeira, including the increased expression of two uncharacterized drug transporters, found to catalyse the extrusion of this drug, thus contributing to increase C. glabrata resistance to 5-FC. These results, just published in Frontiers in Microbiology, are expected to contribute to maintain the usability of this drug in antifungal therapy. Click on title to learn more.

Rejection and colonization by microbes are two problematic issues that often require the surgical removal of medical implants with increased risks for patients. In a recent publication in J. Materials Chemistry B, a team of researchers from iBB-BSRG (Nuno Mira, Diana Cunha), IST and Instituto Politécnico de Setúbal have shown that functionalization of Zn surfaces with ZnO-nanostructured 'Anastacia' flowers (NAF) results in improved biomaterials that can potentially overcome these important drawbacks and further boost the use of Zn in biomedical implants. Colonization of the NAF-coated Zn surface by Candida parapsilosis and Candida albicans, two of the more relevant microbial species colonizing medical devices, was significantly reduced on the NAF-coated Zn surface. The ZnO-derived coating is an expeditious strategy to improve the resilience of Zn-based resorbable biomaterials towards Candida spp. colonization, paving the way for the design of bioactive ZnO-derived coatings with potential for clinical applications on bone. Click on title to learn more. 

Photo: ZnO flowers with yeast cells.

In a recent paper published in Cell Cycle, a BSRG-iBB team led by Arsénio Fialho shows how the bacterial protein azurin modulates the plasma membranes’ biophysical properties of the lung adenocarcinoma A549 cancer cells. In collaboration with the group of Nuno Santos at IMM, and Fábio Fernandes (CQFM- IST), changes are detected through the nanoindentation of cells detected by Atomic Force Microscopy (AFM). AFM is a technique with increased importance in detecting and quantifying these changes, namely on elasticity and deformability which are then related to several cell processes such as adherence, signaling, invasion and proliferation. By causing such changes, azurin contributes to the sensitization of A549 cells to EGFR-targeted therapies, to which they are resistant, possibly improving the outcome of these clinical therapies in patients that may develop resistance.

Acetic acid accumulation inhibits yeast growth and fermentation, impairing many yeast-based biotechnological processes, in particular lignocellulosic biorefineries. A recent study published in Biochemical Journal, performed by BSRG-iBB researchers led by Prof. Isabel Sá-Correia and started in the framework of the PhD in Biotechnology and Bioscience of Joana Guerreiro, in collaboration with researchers from Jeremy Thorner´s Lab at University of California, Berkeley, demonstrated that acetic acid tolerance requires sphingolipid biosynthesis. This process is mediated by the TORC2-dependent Ypk1 kinase, a key regulator of the sphingolipid biosynthetic pathway. It was thus proposed the manipulation of the flux into the sphingolipid biosynthetic pathway as a novel rational way to increase acetic acid tolerance of industrial yeast strains.

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Despite very good safety records, clinical trials using plasmid DNA have failed due to low transfection efficiency and brief transgene expression. One of the reasons for this failure is poor plasmid design. In a paper published in Biotechnology and Genetic Engineering Reviews, researchers from iBB-BERG led by Gabriel Monteiro review critical aspects of plasmid design including promoter, polyadenylation signal, codon optimization and/or insertion of introns or nuclear-targeting sequences. The impact of detrimental elements like CpG motifs, selection markers, origins of replication, cryptic eukaryotic signals or nuclease-susceptible regions and inverted repeats is also examined. Click on title to learn more.

Photo details: CHO cells transfected with plasmid vector coding for GFP.