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A 3d cell culture model of the tuberculosis granuloma that can be applied for h...

David, Susana; Mandal, Manoj; Anes, Elsa; Pires, David

Introduction: The granuloma is an inflammatory infiltrate of mononuclear cells. Some bacterial infections are characterized by the formation of granulomas as part of the immune response to contain the infection. Granuloma models have contributed valuable insights into the genetic basis of granuloma formation during infection. For example, IFNGR1 and IFNGR2 variants have been found to disrupt the immune response...


Host-directed therapies based on protease inhibitors to control Mycobacterium t...

Mandal, Manoj; Pires, David; Azevedo-Pereira, Jose Miguel; Anes, Elsa

Despite continuous and extensive global efforts in the fight against tuberculosis (TB), this infectious disease continues to exert a tremendous burden on public health concerns and deaths worldwide. TB, caused by the bacterial species Mycobacterium tuberculosis, is highly frequent in people living with HIV. The continuing epidemics of both chronic infections and the emergence of antimicrobial resistance, as wel...


Ethambutol and meropenem/clavulanate synergy promotes enhanced extracellular an...

Olivença, Francisco; Pires, David; Silveiro, Cátia; Gama, Bianca; Holtreman, Frederico; Anes, Elsa; Catalao, Maria João

Increasing evidence supports the repositioning of beta-lactams for tuberculosis (TB) therapy, but further research on their interaction with conventional anti-TB agents is still warranted. Moreover, the complex cell envelope of Mycobacterium tuberculosis (Mtb) may pose an additional obstacle to beta-lactam diffusion. In this context, we aimed to identify synergies between beta-lactams and anti-TB drugs ethambut...


Cystatin F depletion in Mycobacterium tuberculosis-infected macrophages improve...

Mandal, Manoj; Pires, David; Calado, Marta; Azevedo-Pereira, Jose Miguel; Anes, Elsa

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in activating the perforin/granzyme cytotoxic pathways. It is targeted at the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CstF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loa...


Synthesis, activity, toxicity, and in silico studies of new antimycobacterial N...

Pais, João P.; Antoniuk, Olha; Pires, David; Delgado, Tiago; Fortuna, Andreia; Costa, Paulo J.; Anes, Elsa; Constantino, Luis

Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-β-D-ribofuranose 2′-oxidase (DprE1), an essential Mycobacterium tuberculosis (Mtb) enzyme and an emergent antitubercular target. Hereby, we ...


Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammati...

Calado, Marta; Ferreira, Rita; Pires, David; Santos-Costa, Quirina; Anes, Elsa; Brites, Dora; Azevedo-Pereira, José Miguel

Since the identification of human immunodeficiency virus type 1 (HIV-1) in 1983, many improvements have been made to control viral replication in the peripheral blood and to treat opportunistic infections. This has increased life expectancy but also the incidence of age-related central nervous system (CNS) disorders and HIV-associated neurodegeneration/neurocognitive impairment and depression collectively refer...


Role of type I interferons during Mycobacterium tuberculosis and HIV infections

Anes, Elsa; Azevedo-Pereira, José Miguel; Pires, David

Tuberculosis and AIDS remain two of the most relevant human infectious diseases. The pathogens that cause them, Mycobacterium tuberculosis (Mtb) and HIV, individually elicit an immune response that treads the line between beneficial and detrimental to the host. Co-infection further complexifies this response since the different cytokines acting on one infection might facilitate the dissemination of the other. I...


ESAT-6 a major virulence factor of mycobacterium tuberculosis

Anes, Elsa; Pires, David; Mandal, Manoj; Azevedo-Pereira, José Miguel

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), is one of the most successfully adapted human pathogens. Human-to-human transmission occurs at high rates through aerosols containing bacteria, but the pathogen evolved prior to the establishment of crowded populations. Mtb has developed a particular strategy to ensure persistence in the host until an opportunity for transmission ...



CRISPRi-mediated characterization of novel anti-tuberculosis targets: mycobacte...

Silveiro, Cátia; Marques, Mariana; Olivença, Francisco; Pires, David; Mortinho, Diana; Nunes, Alexandra; Pimentel, Madalena; Anes, Elsa

The lack of effective therapeutics against emerging multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) prompts the identification of novel anti-tuberculosis targets. The essential nature of the peptidoglycan (PG) layer of the mycobacterial cell wall, which features several distinctive modifications, such as the N-glycolylation of muramic acid and the amidation of D-iso-glutamate, makes it a target...


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