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

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

The researchers at HMS discovered that virulent and non-virulent strains of the tuberculosis pathogen(Mycobacterium tuberculosis) both 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, causing M. tuberculosis to infect 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 membrane damage, 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 process of cell membrane repair, which was previously unknown, so the researchers focused on characterizing this process. They found that the protein Rab3a, which had already been described in other contexts, such as neuronal synapses, was shown to play 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 thus becomes active and functional in cell membrane repair by lysosomes.

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

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

Together with iBET, IPOLFG and ITQB-UNL, CEDOC integrates the R&D unit called iNOVA4Heath - Program in Translational Medicine, financed by FCT.

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