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Proteínas imunogénicas contra A. baumannii: recurso para combater multirresistê...

Gomes, Marta; Domingues, Rita Alexandra Carpinteiro; Fraga, Alexandra Gabriel; Oliveira, Hugo Alexandre Mendes

Acinetobacter baumannii é um bactéria nosocomial e multirresistente, considerada pela da Organização Mundial da Saúde (OMS) como prioridade crítica para o desenvolvimento de novas estratégias antibacterianas.A imunização é uma estratégia eficiente para prevenir infeções, como por exemplo, por A. baumannii. As vacinas à base de proteínas têm vantagens sobre vacinas vivas, atenuadas ou inativas, uma vez que têm a...


Bacteriophage depolymerases: evolutionary insights and antivirulence strategies...

Oliveira, Hugo Alexandre Mendes; Pires, Diana Priscila Penso; Melo, Luís Daniel Rodrigues; Mendes, Ana; Fraga, Alexandra Gabriel; Pedrosa, Jorge

To be able to enter and replicate in exopolysaccharide slime or capsule surrounded bacteria, bacteriophages (viruses of bacteria) have evolved the ability to overcome the exopolysaccharides structure by producing virion-associated proteins with polysaccharide depolymerization activities. We have isolated > 20 bacteriophages infecting several species of the Acinetobacter baumannii-Acinetobacter calcoaceticus com...


Increasing the potential of cell-penetrating peptides for cancer therapy using ...

Duarte, Diana; Fraga, Alexandra Gabriel; Pedrosa, Jorge; Martel, Fátima; Vale, Nuno

Cancer treatment is one of the major fields of interest for the scientific community. Investment in cancer research is costly but essential to provide patients with more effective and safe treatments. In this project, we describe the synthesis and characterization of new thiazole derivatives coupled to CPP2, a cell-penetrating peptide (CPP) reported for colon cancer cells. Using a human adenocarcinoma-derived c...


K2 capsule depolymerase is highly stable, is refractory to resistance, and prot...

Oliveira, Hugo Alexandre Mendes; Mendes, Ana; Fraga, Alexandra Gabriel; Ferreira, Alice Maria Fernandes; Pimenta, Andreia I.; Mil-Homens, Dalila

Acinetobacter baumannii is emerging as a major nosocomial pathogen in intensive care units. The bacterial capsules are considered major virulence factors, and the particular A. baumannii capsular type K2 has been associated with high antibiotic resistance. In this study, we identified a K2 capsule-specific depolymerase in a bacteriophage tail spike C terminus, a fragment that was heterologously expressed, and i...


Genetic variation in autophagy-related genes influences the risk and phenotype ...

Capela, C.; Dossou, A. D.; Silva-Gomes, Rita; Sopoh, G. E.; Makoutode, M.; Menino, João Filipe Marques Almeida Ferreira; Fraga, Alexandra Gabriel

Introduction Buruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produ...


IFN-gamma-dependent activation of macrophages during experimental infections by...

Torrado, Egídio; Fraga, Alexandra Gabriel; Logarinho, Elsa; Martins, Teresa G.; Carmona, Jenny A.; Gama, José B.; Carvalho, Maria A.

Buruli ulcer, caused by Mycobacterium ulcerans infections, is a necrotizing skin disease whose pathogenesis is associated with the exotoxin mycolactone. Despite the relevance of this emergent disease, little is known on the immune response against the pathogen. Following the recent demonstration of an intramacrophage growth phase for M. ulcerans, we investigated the biological relevance of IFN-gamma and the ant...


New foci of Buruli ulcer, Angola and Democratic Republic of Congo

Kibadi, Kapay; Panda, Mbutu; Tamfum, Jean-Jacques Muyembe; Fraga, Alexandra Gabriel; Longatto, Adhemar; Anyo, Gladys; Pedrosa, Jorge

We report 3 patients with laboratory-confirmed Buruli ulcer in Kafufu/Luremo, Angola, and Kasongo-Lunda, Democratic Republic of Congo. These villages are near the Kwango/Cuango River, which flows through both countries. Further investigation of artisanal alluvial mining as a risk factor for Buruli ulcer is recommended.


Evidence for an intramacrophage growth phase of Mycobacterium ulcerans

Torrado, Egídio; Fraga, Alexandra Gabriel; Castro, António G.; Stragier, Pieter; Meyers, Wayne M.; Portaels, Françoise; Silva, Manuel T.; Pedrosa, Jorge

Mycobacterium ulcerans is the etiologic agent of Buruli ulcer (BU), an emerging tropical skin disease. Virulent M. ulcerans secretes mycolactone, a cytotoxic exotoxin with a key pathogenic role. M. ulcerans in biopsy specimens has been described as an extracellular bacillus. In vitro assays have suggested a mycolactone-induced inhibition of M. ulcerans uptake by macrophages in which its proliferation has not be...


Mycolactone-mediated inhibition of tumor necrosis factor production by macropha...

Torrado, Egídio; Adusumilli, Sarojini; Fraga, Alexandra Gabriel; Small, Pamela L. C.; Castro, António G.; Pedrosa, Jorge

The pathogenicity of Mycobacterium ulcerans, the agent of Buruli ulcer, depends on the cytotoxic exotoxin mycolactone. Little is known about the immune response to this pathogen. Following the demonstration of an intracellular growth phase in the life cycle of M. ulcerans, we investigated the production of tumor necrosis factor (TNF) induced by intramacrophage bacilli of diverse toxigenesis/virulence, as well a...


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