iBB

B. cenocepacia is a contact-dependent bacterium known for its capacity of causing respiratory infections. Among a panel of adhesins used by B. cenocepacia to contact with host cells, trimeric autotransporter adhesins (TAAs) are of particular interest. In a recent paper published in Cellular Microbiology, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Michelle Kilcoyne and Lokesh Joshi from the National University of Ireland Galway, Galway, Ireland, were able to uncover the roles of the TAA BCAM2418, as an adhesin and the type of host glycans that serve as recognition targets. This work reveals the importance of BCAM2418 as a mediator of early host-bacteria crosstalk.

Cell-based therapies have been showing unprecedented therapeutic potential, already changing the landscape of medical care. Extracellular vesicles are nanoparticles naturally secreted by cells, which are important mediators of intercellular communication in our organism and are able to mediate therapeutic effects from their cells of origin. These vesicles can also be used as drug delivery vehicles to target multiple diseases. In a paper recently published in Frontiers in Cell and Developmental Biology, iBB researchers in collaboration with iMM Lisboa, CQE-IST and the companies PBS Biotech and AventaCell Biomedical, developed a new strategy for the robust and scalable production of extracellular vesicles from mesenchymal stromal cells, using bioreactors and an animal serum-free cell culture supplement. This strategy, developed within the frame of the PhD Program in Bioengineering of Miguel de Almeida Fuzeta, is a relevant step towards the large scale production of extracellular vesicles form different human tissue sources, which are promising tools for the development of new therapies against a variety of diseases, from cardiovascular diseases to cancer.

p28 is a 28 amino acids peptide derived from the bacterial protein azurin. It possesses cell-penetrating capabilities showing preferential enter in cancer cells. Moreover it has been subject in US to two phase I clinical trials as a anticancer agent. In a recent paper published in Journal of Controlled Release, a iBB team (Garizo AR, Dias TP, Fernandes F, Bernardes N, Fialho AM) together with a i3S/UP team (Castro F, Martins C, Almeida A, Barrias CC, Sarmento B) were able for the first time to fabricate p28-functionalized PLGA nanoparticles (NPs) loaded with the EGFR tyrosine kinase inhibitor gefitinib. The results obtained indicate that these NPs interact preferentially with lung cancer cells due to their decoration with p28 peptide. In vitro cytotoxicity assays demonstrate biological activity of the NPs against lung cancer cancer cells. Finally, in vivo studies demonstrated a great potential of the p28-NPs in enhancing the therapeutic effects of gefitinib.

Burkholderia cenocepacia is a human contact-dependent pathogenic bacterium known for its capacity of causing severe opportunistic respiratory infections. B. cenocepacia uses a complex machinery for primary adherence with host cells. In a recent paper published in Scientific Reports, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Marta M Alves from CQE, IST, have developed a RNASeq-based approach that led to identify adhesion candidate genes that were not previously reported in the context of a B. cenocepacia infection. This study presents a innovative technique in which their use Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia.

Cell-based therapies can enhance the specificity of anti-cancer therapeutic agents. In this context, human mesenchymal stromal cells (MSC) hold a promising future as cell delivery systems for anti-cancer proteins due to their innate tropism for tumors. iBB researchers Marília Silva, Gabriel Monteiro, Arsénio Fialho, Nuno Bernardes and Cláudia Lobato da Silva, engineered human MSC through non-viral methods to secrete a human codon-optimized version of azurin (hazu), a bacterial protein with demonstrated anti-cancer activity towards different cancer models in vitro and in vivo. Upon treatment with conditioned media (CM) from these engineered cells, a decrease in cancer cell proliferation, migration and invasion was seen, and an increase in cell death was observed for breast and lung cancer cell models. The results achieved by SCERG- and BSRG-iBB researchers were published in Frontiers in Cell and Developmental Biology, Stem Cell Research section.

https://www.scoop.it/t/ibb/?&tag=Ars%C3%A9nio+FialhoUnlike the current paradigm of “one drug one target”, nowadays multiple-target approaches taking place at the cancer cell membrane are gaining much more relevance. The rational is based on the use of a new class of molecules that can exert significant changes in the dynamics and organization of cell membranes thereby affecting growth factor signaling, invasiveness and drug resistance. In a review published in a Special Issue “Receptor-Targeted Cancer Therapy” of the International Journal of Molecular Sciences, BSRG-iBB team members Nuno Bernardes and Arsenio M Fialho present and discuss novel approaches for cancer therapy, including the anticancer bacterial protein azurin.