Portuguese research paves the way for the treatment of tuberculosis and related diseases

The scientific journal Journal of Cell Biology recently published a study led by two researchers from the Center for Chronic Disease Studies (CEDOC), part of NOVA Medical School, Faculty of Medical Sciences, NOVA University Lisbon. The research describes the role of a protein complex that is fundamental to the cell membrane repair process in the context of tuberculosis infection and other chronic diseases. The work was chosen to be included in the Faculty1000 list, which brings together articles of high importance and potential.

The study originated from the finding by HMS researchers that both virulent and non-virulent strains of the tuberculosis pathogen (Mycobacterium tuberculosis) cause infection, although they use different mechanisms. In both virulent and non-virulent strains, the infection causes damage to the host cell membrane and cell death. In the case of infection with the virulent form of the pathogen, the cell is unable to repair the damage to the membrane, leading to M. tuberculosis infecting neighboring cells, spreading the infection, and causing fulminant tuberculosis. On the other hand, in the case of infection with non-virulent strains, the cells also suffer damage to the membrane, but are able to repair this damage, so that the infected cell dies but the microorganism does not spread to neighboring cells.

The discovery made in this study focuses on identifying the machinery involved in this cell membrane repair process, which was previously unknown, so the researchers focused on characterizing this process. They discovered that the Rab3a protein, which had already been described in other contexts, such as neuronal synapses, plays an essential role in cell membrane repair, since in the absence of this protein, repair is inhibited. To function, Rab3a needs to recruit effectors, i.e., other proteins that bind to it, forming a protein complex that becomes active and functional in cell membrane repair by lysosomes.

This advance in knowledge can be applied to tuberculosis, but also to other contexts in which cell membrane damage occurs, such as physical exercise. It could also be used in the context of some rare lysosomal storage disorders, to enable the development of new therapies based on the release of the lysosomal contents that cause these diseases outside the cell.

Otília Vieira and Duarte Barral, researchers at CEDOC, led this study, which involved collaboration with researchers from the University of Coimbra and Harvard Medical School (HMS), and was funded by the Harvard Medical School – Portugal Program.

CEDOC, together with iBET, IPOLFG, and ITQB-UNL, is part of the R&D unit called iNOVA4Heath – Translational Medicine Program, funded by FCT.

Source: NOVA Medical School | Faculty of Medical Sciences.
Image: Schematic model of the cell membrane repair process.