iBB
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Institute for Bioengineering and Biosciences
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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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Controlling Biofilm Establishment Since the First Touch

Controlling Biofilm Establishment Since the First Touch | iBB | Scoop.it

Candida glabrata’s ability to cause human infections is tightly linked to its impressive ability to form persistent biofilms. The molecular control of this process is far from being clarified, as it lacks many of the typical features displayed by other Candida species. In this study, a combination of genetic screening, RNA-seq based transcriptomics, and Single-Cell Force Spectroscopy (SCFS), enabled the observation that the transcription factor CgEfg1, but not CgTec1, is necessary for the initial interaction of C. glabrata cells with both abiotic surfaces used in medical devices and epithelial cells, while both transcription factors orchestrate biofilm maturation. The knowledge gathered through this study by former PhD student Mafalda Cavalheiro, and an international team led by Miguel Cacho Teixeira, BSRG-iBB, including Etienne Dague, LAAS-CNRS, Geraldine Butler, University College Dublin, and Arsénio Fialho, BSRG-iBB, and just published in Communications Biology, is expected to contribute to guide the design of more successful therapeutic approaches.

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Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles

Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles | iBB | Scoop.it

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.

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Galleria mellonella as an Animal Model to Test the Activity of Synthetic Phages Against P. aeruginosa Infections

Galleria mellonella as an Animal Model to Test the Activity of Synthetic Phages Against P. aeruginosa Infections | iBB | Scoop.it

Bacteriophages have emerged as a promising therapeutic approach to deal with the problem of antibiotic resistance. In a study led by researchers from University of Minho and co-authored by Dalila Mil-Homens and Arsénio M Fialho from BSRG-iBB, the advantages of using a non-mammalian animal model - the larvae of the greater wax moth Galleria mellonella) - to test the efficacy of bacteriophages to treat bacterial infections was demonstrated. Specifically, the animal model was used to assess the antibacterial efficacy of wild-type and synthetic phages with reduced Genomes against the bacterium P. aeruginosa. This model of infection was implemented at our laboratory and efforts are continually being made to improve and turning it more accurate and robust. The work was published in Scientific Reports.

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Potential of Azurin as an Anti-SARS-CoV-2 Agent Unveiled by Molecular Simulation

Potential of Azurin as an Anti-SARS-CoV-2 Agent Unveiled by Molecular Simulation | iBB | Scoop.it

Several studies have shown that the bacterial protein azurin and its derived peptide p28, can serve as a source for the development of emerging therapeutic drugs to treat cancer as well as against various infectious agents, such as viruses and parasites. Based on that, Arsenio M Fialho started collaboration with two Indian partners aiming to study the feasibility of using azurin and its derived peptide p28 as a protein-peptide-based strategy to inhibit/block SARS-CoV-2 infections. So far, based on a molecular docking and molecular dynamics simulations study, we observed that azurin and particularly the p28 peptide interact with SARS-CoV-2- spike (S) receptor-binding domain and form stable complexes. This work has been published in the Journal of Biomolecular Structure and Dynamics.

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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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Burkholderia cenocepacia–Host Cell Contact Controls Transcription Activity of the Trimeric Autotransporter Adhesin Gene

Burkholderia cenocepacia–Host Cell Contact Controls Transcription Activity of the Trimeric Autotransporter Adhesin Gene | iBB | Scoop.it

Burkholderia cenocepacia is a human contact-dependent pathogenic bacterium known for its capacity of causing severe and persistent opportunistic respiratory infections. The initial contact between bacteria and the human epithelial cells are crucial for the success of the infection. B. cenocepacia uses very complex machinery for primary adherence with host cells. Among those, the class of trimeric autotransporter adhesins (TAAs) deserves particular attention. In this study, published in MicrobiologyOpen, BSRG-iBB researchers Andreia Pimenta, Dalila Mil-Homens and Arsénio M. Fialho demonstrated that BCAM2418, a TAA from the epidemic strain B. cenocepacia K56-2, shows an on–off switch after an initial colonization period, exhibits a strong expression dependent on the host cell type, and enhances its function on cell adhesion. Moreover, this study found that overexpression of BCAM2418 gene contributes to the bacterial cell adhesion to host cells and is dependent on recognition of O‐linked glycans from the host cell membranes. Overall, this study not only defines the behavior of this particular TAA during the step of bacterial adhesion but also provide insights aiming to determine potential targets for therapeutic proposals.

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Perturbing the Dynamics and Organization of Cell Membrane Components: A New Paradigm for Cancer-Targeted Therapies

Perturbing the Dynamics and Organization of Cell Membrane Components: A New Paradigm for Cancer-Targeted Therapies | iBB | Scoop.it

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.

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"The Admirable World of Microbes": A Training Course for Secondary School Teachers

"The Admirable World of Microbes": A Training Course for Secondary School Teachers | iBB | Scoop.it

A training course for secondary school teachers entiled "The admirable world of Microbes: small in size, great in action" was carried out at Instituto Superior Técnico (IST) on the 17 and 22 september within the frame of the commemorations of the International Microorganism Day 2018. The course was accredited by the Training Center of the Ordem dos Biólogos (OB) and aimed at updating and reinforcing theoretical knowledge and practical skills in the area of Microbiology and Biotechnology. The 12-hour training included theoretical (4 hours), computational (2 hours) and laboratory (4 hours) modules as well as a roundtable discussion (2 hours). The course was organized and taught by Arsénio Fialho, Cristina Viegas and Leonilde Moreira from the Bioengineering Department of IST and BSRG-iBB. It was attended by 22 teachers from schools all over the country. The initiative was supported by the Portuguese Society of Microbiology (SPM), OB and IST.

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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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Repair of Iron Centers Protein Contributes to the Virulence of Staphylococcus aureus

Repair of Iron Centers Protein Contributes to the Virulence of Staphylococcus aureus | iBB | Scoop.it

RICs are a family of bacterial proteins involved in the repair of iron center-containing proteins damaged by antimicrobial reactive species liberated by the innate immune system of infected hosts. In a recent paper published in the journal Virulence, researchers from BSRG-iBB (Dalila Mil-Homens and Arsénio M. Fialho) have collaborated with the group of Lígia M. Saraiva from ITQB NOVA, to unveil the role played by RIC protein in S. aureus pathogenesis. More specifically, culture macrophages, human lung epithelial cells and an animal infection model (the larvae of the greater wax moth Galleria mellonella) were used to investigate the virulence of wild-type S. aureus vs ric mutant. Altogether, the data show that RIC is important for the virulence of S. aureus. Click on title to learn more.

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Determining Virulence in Candida glabrata Through Adaptation to Host Stress

Determining Virulence in Candida glabrata Through Adaptation to Host Stress | iBB | Scoop.it

Persistence and virulence of Candida glabrata infections are multifactorial phenomena, whose understanding is crucial for infection erradication. In this study, the multidrug transporter CgDtr1 was found to be a plasma membrane acetic acid exporter, relieving the stress induced upon C. glabrata cells within hemocytes, and thus enabling increased proliferation and virulence against G. mellonella larvae. These results, emerging from a collaboration between BSRG members and led by Miguel Cacho Teixeira, were just published in Frontiers in Cellular and Infection Microbiology and are expected to contribute to design more suitable therapeutic strategies. Click on title to learn more.

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US Patent Application on Cupredoxins Published

US Patent Application on Cupredoxins Published | iBB | Scoop.it

A US Patent application (application number 14/817063) co-authored by Arsénio Fialho from BSRG-iBB and by researchers from the University of Illinois headed by Prof. Ananda Chakrabarty has just been published. The innvention relates to compositions and methods of use of cupredoxins, and variants, derivatives and structural equivalents of cupredoxins that interfere with the ephrin signaling system in mammalian cells. Specifically, the invention relates to uses of cupredoxins, such as azurin, rusticyanin and plastocyanin, and variants, derivatives and structural equivalents thereof, to treat cancer in mammals. Click on title to learn more. 

Photo: 3D model of Rusticyanin from Thiobacillus ferrooxidans.

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Gefitinib-Loaded p28-PLGA Nanoparticles Reduce Tumor Burden and Metastases in Lung Cancer

Gefitinib-Loaded p28-PLGA Nanoparticles Reduce Tumor Burden and Metastases in Lung Cancer | iBB | Scoop.it

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.

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Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion

Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion | iBB | Scoop.it

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.

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AntiMicrobial Peptide Resistance Conferred by a Polyamine Transporter: a New Virulence Mechanism

AntiMicrobial Peptide Resistance Conferred by a Polyamine Transporter: a New Virulence Mechanism | iBB | Scoop.it

Cellular components that contribute to both pathogenesis and drug resistance are among the most promising drug targets in human pathogens. In this study, the uncharacterized drug:H+ antiporter CgTpo4 was shown to play a role in Candida glabrata virulence in the infection model G. mellonella. The underlying mechanism was demonstrated to include a role in AntiMicrobial Peptide (AMP) resistance, compatible with the observed immune response deployed by G. mellonella upon C. glabrata infection. These results, emerging from a collaboration between BSRG members, led by Miguel Cacho Teixeira and including Arsénio Fialho and Dalila Mil-Homens, were just published in International Journal of Molecular Sciences and are expected to contribute to design more suitable antifungal therapeutic strategies.

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Andreia Pimenta to Defend PhD Thesis in Biotechnology and Biosciences

Andreia Pimenta to Defend PhD Thesis in Biotechnology and Biosciences | iBB | Scoop.it

Andreia Isabel de Melo Pimenta will be defending her PhD thesis in Biotechnology and Biosciences at Instituto Superior Técnico, Tuesday the 22nd of December 2020, at 10:00 am (https://videoconf-colibri.zoom.us/j/87589426644). During the last years, and under the supervision of Arsénio Fialho from BSRG-iBB, Andreia studied the role of Trimeric autotransporter adhesins in the pathogenesis of Burkholderia cenocepacia. The title of her thesis is “New insights into the interaction of Burkholderia cenocepacia with host cells: Trimeric autotransporter adhesins as pathogenicity factors”.

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Conditioned Medium from Azurin-expressing MSC Demonstrates Anti-tumor Activity

Conditioned Medium from Azurin-expressing MSC Demonstrates Anti-tumor Activity | iBB | Scoop.it

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.

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Arsénio Fialho Joins Editorial Board of Bioengineered

Arsénio Fialho Joins Editorial Board of Bioengineered | iBB | Scoop.it

Arsenio M Fialho has joined the Editorial board of Bioengineered (Taylor and Francis Ltd) as an Associate Editor with a two-year term beginning June 1st 2020. Bioengineered is an open access, multi-disciplinary journal dedicated to publishing all aspects of bioengineering and biotechnology. Arsénio is a senior researcher at BSRG-iBB and his research is focused on the study of bacterial proteins as novel anticancer agents.

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Phage-encoded K2 Capsule Depolymerase Protects Larvae and Mice from Acinetobacter baumannii Sepsis

Phage-encoded K2 Capsule Depolymerase Protects Larvae and Mice from Acinetobacter baumannii Sepsis | iBB | Scoop.it

Acinetobacter baumannii is an important nosocomial pathogen resistant to many antibiotics. The relevance of a bacteriophage capsular depolymerase as a therapeutic agent against A. baumannii has now been unveiled by a collaborative work between researchers from BSRG-iBB (Dalila Mil-Homens, Andreia Pimenta, Arsénio M. Fialho) and the group of Joana Azeredo from the University of Minho. The greater wax moth Galleria mellonella and mice were used as animal models to address the therapeutic efficacy of the depolymerase against the infection. Results show that the enzyme makes bacterial cells fully susceptible to the host complement system killing effect. The depolymerase characterized here fits the new trend of alternative antibacterial agents needed against multidrug resistant pathogens. The work was published in Appl. Environ. Microbiol.

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Following the Evolution Towards Fluconazole Resistance in C. glabrata

Following the Evolution Towards Fluconazole Resistance in C. glabrata | iBB | Scoop.it

The effectiveness of Candida glabrata as an emerging human pathogen relies on its ability to acquire azole drug resistance. In a paper just published in Antimicrobial Agents and Chemotherapy, the first time-course evaluation of the global gene expression changes that lead a drug susceptible C. glabrata clinical isolate to step-wise acquisition of resistance to azole drugs was conducted. This work, which results from the collaboration of six different teams under the coordination of Miguel C Teixeira from BSRG-iBB, highlights the multifactorial nature of azole resistance acquisition, including the Epa3 adhesin as a new player, while providing fascinating clues on the underlying evolutionary path. This knowledge is of crucial importance to design more effective antifungal therapy.

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Microbial Infections and Cancer Therapy

Microbial Infections and Cancer Therapy | iBB | Scoop.it

The book "Microbial Infections and Cancer Therapy", co-edited by Arsénio Fialho from BSRG-iBB in collaboration with Ananda Chakrabarty (University of Illinois) has just been released by Pan Stanford Publishing. The book deals with the emerging concept that certain pathogenic bacteria and viruses, when infecting people with cancer, actively fight tumors, allowing their regression. It features 12 chapters written by pioneers in microbial, biotech, and cancer research and covers the emerging roles of various microorganisms and their products in cancer therapy. The book highlights the benefits of using conventional cancer treatments (such as chemo- and radiotherapies) with microbial-based therapies.

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Nuno Bernardes Wins Poster Prize at 3rd ASPIC Congress

Nuno Bernardes Wins Poster Prize at 3rd ASPIC Congress | iBB | Scoop.it

iBB researcher Nuno Bernardes was awarded one of the Poster Prizes sponsored by the European Association for Cancer Research at the 3rd Congress of ASPIC - Associação Portuguesa de Investigação em Cancro. The work entitled “Modulation of membrane properties and interaction with lipid rafts components GM-1 and caveolin-1 in cancer cells by azurin increases membrane fluidity and sensitivity to anti-cancer drugs” was developed at BSRG-iBB, led by Prof. Arsénio Fialho in collaboration with colleagues from the CQFM-IST, Sandra N Pinto and Fábio Fernandes.

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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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BcaA Adhesin Binds TNFR1 and Contributes to Induce Airway Inflammation

BcaA Adhesin Binds TNFR1 and Contributes to Induce Airway Inflammation | iBB | Scoop.it

Burkholderia cenocepacia has emerged as a prominent opportunistic pathogen causing acute airways infections in cystic fibrosis patients. To initiate infection, B. cenocepacia must be able to colonize the respiratory epithelium, a step mediated by adhesins. In a study published in Cell Microbiology, BSRG-iBB researchers Dalila Mil-Homens and Arsénio Fialho, in collaboration with Sandra Pinto from CQFM (Lisbon) and Cecília Arraiano group from ITQB (Lisbon), demonstrated that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a TNFR1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Moreover, this study reinforced the multifunctional nature of BcaA and was the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during bacterial infections. Click on title to learn more.

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