iBB

A wide variety of enzymatic pathways producing specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, in a recent publication in Nature Chemical Biology, an international consortium of researchers, including Leonilde M. Moreira from BSRG-iBB, proposed the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard (http://mibig.secondarymetabolites.org/). MIBiG will empower next-generation research on the biosynthesis, chemistry and ecology of broad classes of societally relevant bioactive secondary metabolites, guided by robust experimental evidence and rich metadata components. Click on title to learn more.

The taxonomy of Burkholderia cepacia complex (Bcc) has recently evolved significantly. The novel species B. contaminans and B. lata were proposed for a divergent group of bacteria formerly classified as B.cepacia recA K. In a recent publication in the Journal of Medical Microbiology, Carla Coutinho and Isabel Sá-Correia from BSRG-iBB, together with researchers from Hospital de Santa Maria (HSM) in Lisbon, have re-examined the taxonomic position, at the species level, of several isolates previously classified as B. cepacia recA K from a Bcc collection and also extended the identification to other isolates retrieved from CF patients under surveillance at the major Portuguese CF Center at HSM. During 15 years of epidemiological surveillance of respiratory infections involving Bcc in this Portuguese CF Center, B. contaminans was found to be involved in chronic and transient infections or to have been eradicated. The clinical outcome of the infected patients under study provided new information on the clinical impact of the rarely found B. contaminans species in CF respiratory infections. Click on tile to learn more.

In a recent publication in Biotechnology Journal researchers from the Stem Cell Bioengineering and Regenerative Medicine Laboratory (SCBL) at BERG-iBB describe a novel methodology capable of providing patient-specific neural cells under defined conditions using vitronectin and dual SMAD inhibition. The authors show how pluripotent stem cells can be used to generate patient-specific neural cells that could be used to gain a better understanding of disease mechanisms. This ability to recapitulate the development of the human nervous system in vitro could provide important insights on the mechanisms involved in the maturation of specific neural cell types, making this approach transversal to other related areas in neurodevelopmental research.

The quest for renewable fuels from sustainable and ecologically friendly processes has identified biodiesel as a promising candidate. Carla de Carvalho and Maria  Cortes of BERG-iBB recently showed that bacterial cells of Rhodococcus erythropolis DCL14 and R. opacus PWD4 can accumulate triacylglycerols, the most relevant lipids for biodiesel production, and other lipids which contain fatty acids that may be esterified. Appropriate growth conditions, such as N and P limitation, increased lipid accumulation in the cells. The cetane numbers of the fatty acid blends produced, which measure the quality of diesel fuels and biodiesel, are in accordance to biodiesel standards.

Heparin is a naturally occurring sulfonated glycosaminoglycan, characterized by a high density and distribution of negative charges that is widely used as an injectable anticoagulant. In a recent pubication, BERG-iBB researchers led by Ana Azevedo explore the strong cation exchanger potential of an heparin resin, namely its  ability to capture a basic mAb from CHO cell culture supernatants. The performance of the proposed capture step was estimated in terms of yield, protein purity and purification factor, and compared to the traditional protein A affinity chromatography.

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5-Flucytosine is currently used as an antifungal drug in combination therapy, but fungal pathogens are rapidly able to develop resistance against this drug, compromising its therapeutic action. The understanding of the underlying resistance mechanisms is crucial to deal with this problem. In a recent paper published in PLoS ONe by BSRG-iBB researchers, the S. cerevisiae knockout collection was screened for increased resistance to flucytosine. Base on this chemogenomics analysis, further studies were conducted in the pathogenic yeast Candida glabrata, leading to the discovery of new mechanisms of 5-flucytosine resistance, including cell wall remodeling and decreased drug accumulation mediated by the action of the aquaglyceroporins CgFps1 and CgFps2.

Pharmaceutical excipients have different functions within a drug formulation and can influence the manufacturability and/or performance of medicinal products.  Sometimes it may be necessary to qualify a second supplier, but its product will not be completely equal to the first supplier product. In a recent study co-authored by José Cardoso Menezes from BERG-iBB, Multivariate Analysis is used to extract relevant information  from Raman spectroscopy, laser diffraction and Xray powder diffraction analysis of calcium hydrogen phosphate from two suppliers. The two lots of CaHPO4 could be discriminated by their supplier and the  gained knowledge made it possible to specify an enhanced strategy for second supplier qualification. Click on title to learn more. 

Pseudomonas aeruginosa causes chronic lung infections in people with cystic fibrosis (CF) and acute opportunistic infections in people without CF. In a recently published article, an international consortium of researchers, members of the EU COST Action BM1003: Microbial cell surface determinants of virulence as targets for new therapeutics in cystic fibrosis, including Isabel Sá-Correia from BSRG-iBB and the students of the IST PhD programme in Biotechnology and Biosciences, Rita F. Maldonado, Ana S. Moreira, collated forty two P. aeruginosa strains from a range of clinical and environmental sources into a single reference strain panel to harmonise research on this diverse opportunistic pathogen .The panel strains were characterized for growth rates, motility, virulence in the Galleria mellonella infection model, pyocyanin and alginate production, mucoid phenotype, lipopolysaccharide (LPS) pattern, biofilm formation, urease activity, antimicrobial and phage susceptibilities. Overall, the full phenotypic characterization of the defined panel of P. aeruginosa strains increased the current  understanding of the virulence and pathogenesis of P. aeruginosa and may provide a valuable resource for the testing of novel therapies against this problematic pathogen. Click on title to learn more.

Photo details: SEM of Pseudomonas aeruginosa. CDC/ Janice Haney Carr, Public domain. 

The metal imbalance in fish caused by water pollution is thought to play a critical role in neurodegeneration and neuronal dysfunctions. In a recent publication in Metallomics, Teresa Pinheiro from BSRG-iBB, together with researchers from IPMA, CESAM and CIMAR have examined the elemental distributions in brains of wild Liza aurata a teleost fish captured in polluted and reference coastal systems in the vicinity of Lisbon. This study evaluates major and trace elemental contents, essential and toxic, and their compartmentalization in optic lobe structures providing insights into species physiological requirements and vulnerability to metal toxicity. This is the first multi-elemental mapping of neuronal tissue of teleost fish.

Mycobacteria are associated to several diseases, including tuberculosis, but little is known about their behavior in natural ecosystems. In an international study involving Ricardo Santos from Laboratório de Análises, Carla C.C.R. de Carvalho from iBB-BERG and researchers from the Queen’s University Belfast, it was showed that mycobacteria have solute tolerances close to those of eukaryotes. The Mycobacterium strains isolated from Yellowstone and Glacier National Parks (USA), grew at a temperature range of >60ºC, in super-saturated concentrations of hydrophobic stressors and under osmotic stress and chaotropic activity. The study demonstrates that certain mycobacteria strains are as resilient to key solute induced stresses as some of the most stress-tolerant microbes known to science. Click on title to learn more. 

The therapeutic use of human mesenchymal stem/stromal cells (MSC) for a wide range of diseases is at the front line of stem cell-based cellular therapies. Through a bioprocess engineering approach, researchers at BERG-iBB led by Cláudia Lobato Silva and Joaquim Cabral, were able to maximize the production of MSC from different human sources – bone marrow and adipose tissue - in a microcarrier-based stirred culture system. The advances, reported in a recent paper on Biotechnology Journal, clearly improve the scalability and cost-effectiveness of MSC manufacturing, while facilitating the translation to a Good Manufacturing Practices (GMP)-compliant bioprocess.

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Aerobic granular sludge (AGS) is a compact and energy-saving biotechnology pointed as the next generation of wastewater treatment. In a recent publication, BERG-iBB and BSRG-iBB researchers led by Nídia Lourenço compare the performance of AGS with conventional activated sludge in the treatment of textile industry wastewater. High efficiencies were attained in both systems, with AGS providing higher yields and excellent biomass settling properties. Yeast-based toxicity assays also highlighted the better wastewater detoxification performance of AGS, supporting its potential application for industrial wastewater treatment as an effective alternative to the conventional technology based on floc-forming bacteria.

Microreactors have been gaining increased relevance as preferred process intensification tools. Microreactors present several advantages over conventional batch reactors, namely mass and heat transfer, high surface to volume ratios, minute consumption of chemicals, ease of automation and better process control. Within the scope of this exciting area of research, Pedro Fernandes and Filipe Carvalho from BERG-iBB recently designed, assembled and run a low-cost continuous flow enzyme microreactor, allowing for detailed characterization of biocatalytic systems with immobilized enzymes in particulate form. Moreover, the microreactor enabled continuous enzymatic sucrose hydrolysis for 1 month, with sustained substrate conversion of roughly 100%.