iBB
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Institute for Bioengineering and Biosciences
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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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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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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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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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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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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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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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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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Antibacterial Activity of Fish Oils Against Burkholderia and Pseudomonas

Antibacterial Activity of Fish Oils Against Burkholderia and Pseudomonas | iBB | Scoop.it
Natural polyunsaturated fatty acids have been gaining relevance as antimicrobial agents. In a study published in the Journal of Applied Microbiology, BSRG-iBB researchers Dalila Mil-Homens and Arsénio Fialho, together with Suzana Ferreira-Dias from Instituto Superior de Agronomia, have investigated the antimicrobial effects of fish oil-based formulas rich in omega-3 fatty acids (free fatty acids, ethyl esters or triacylglycerols), against cystic fibrosis pathogens Burkholderia cenocepacia and Pseudomonas aeruginosa. The therapeutic and prophylactic potential in vivo of the fish oils was assessed using a Galleria mellonella caterpillar model of infection. The results obtained demonstrate that commercial fish oils, particularly the free form of essential omega-3 fatty acids EPA and DHA, has in vitro and in vivo potent antibacterial activity against B. cenocepacia and P. aeruginosa clinical isolates.

Photo details: SEM of Burkholderia cepacia. CDC/ Janice Haney Carr, Public domain.
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