Percorrer por autor "Vieira, Otilia V."
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- Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infectionsPublication . Calado, Rita D.A.; Mendes, Bárbara B.; Conniot, João; Ravasco, João M.J.M.; Sobral, Daniel; Ferreira, Carolina; Ferreira, Rita; Rodrigues, João Carlos; Santos, Daniela; Duarte, Sílvia; Vieira, Luís; Inácio, Ângela S.; Carrêlo, Henrique; Vaz, Winchil L.C.; Gomes, João Paulo; Nunes, Alexandra; Conde, João; Vieira, Otilia V.Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C12PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C12PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.
- Rab10 regulates phagosome maturation and its overexpression rescues Mycobacterium-containing phagosomes maturationPublication . Cardoso, Carla M. P.; Jordão, Luísa; Vieira, Otilia V.Phagosome maturation follows a defined biochemical program and, in the vast majority of cases, the microbe inside the phagosome is killed and digested. Although, an important number of pathogens, including Mycobacterium tuberculosis, which kills around two million people every year, have acquired the ability to survive, and even replicate by arresting phagosomal maturation. To identify more of the machinery involved in phagocytosis and phagosomal maturation, we investigated the function of Rab10 in engulfment and maturation of inert particles and Mycobacterium bovis bacille Calmette-Guérin (BCG). We showed that Rab10 association with phagosomes is transient and confocal microscopy revealed detectible levels of Rab10 on phagosomal membranes at very early time-points, occurring even before Rab5 acquisition. Rab10 recruitment had strong functional consequence, as the knockdown of endogenous Rab10 by RNA interference or overexpression of Rab10 dominant-negative mutant delayed maturation of phagosomes of IgG-opsonized latex beads or heat killed-mycobacteria. These results can be explained, at least in part, by the involvement of Rab10 in recycling of some phagosomal components. More importantly, overexpression of the constitutively active mutant of Rab10 partially rescued live-Mycobacterium-containing phagosomes maturation. Indeed, we found that the membrane harbouring Mycobacterium acquired early endosome antigen 1 (EEA-1), a marker excluded from phagosomes in control cells. Altogether these results indicate that Rab10, acting upstream of Rab5, plays a prominent role in phagolysosome formation and can modulate Mycobacterium-containing phagosomes maturation.
- Rab8 is required for phagocytosis and phagosomal maturationPublication . Jordão, Luísa; Ramalho, Jose; Seabra, Miguel; Vieira, Otilia V.
- Tuberculosis: new aspects of an old diseasePublication . Jordão, Luísa; Vieira, Otilia V.Tuberculosis is an ancient infectious disease that remains a threat for public health around the world. Although the etiological agent as well as tuberculosis pathogenesis is well known, the molecular mechanisms underlying the host defense to the bacilli remain elusive. In this paper we focus on the innate immunity of this disease reviewing well-established and consensual mechanisms like Mycobacterium tuberculosis interference with phagosomematuration, less consensual mechanism like nitric oxide production, and new mechanisms, such as mycobacteria translocation to the cytosol, autophagy, and apoptosis/necrosis proposed mainly during the last decade.