Discovery of targets to fight bacteria responsible for lung infections

The discovery, published this month in the prestigious journal Scientific Proceedings of the US National Academy of Sciences, reveals details about the biogenesis of rare polysaccharides involved in the construction of the wall of these environmental bacteria, very common in the distribution networks of Labor with these two research teams, with the participation of a group of the Institute of Technology of the biological chemistry of the new University of Lisbon, takes an important step in the fight against diseases caused by these diseases. bacteria – extremely resistant to adverse environmental conditions to disinfectants and most antibiotics – and increasingly common in people with weakened immune systems, including chronic patients and / or the elderly.

Five years later, we understood how methyl mannose polysaccharides (MMPs) were produced by mycobacteria, to try to explain how they contribute to the strength of your wall. "Understanding how mycobacteria build this unique protective wall may be the key to" knocking it over. "We started by identifying the genes and functions of the enzymes involved in the production of the polysaccharide whose characterization at the level of Molecular has revealed its mechanism, which brings us a little closer to the process of inhibition of the process to thereby weaken the wall of these mycobacteria, which makes it its weak point ", explains Nuno Empadinhas, researcher at the CNC. According to the scientist, the first step of the MMP badembly chain has been deciphered and the enzyme responsible, an absolutely unique methyltransferase, has been characterized in detail.

Determination by the i3S / IBMC team of the three-dimensional structure. of this unusual methyltransferase, in parallel with the biochemical characterization of the CNC, revealed in detail the mechanism of its functioning, which could be fundamental for the future design of high-precision antibiotics . Using a combination of biophysical techniques and computer simulations, the i3S / IBMC team "has established a detailed molecular and atomic picture of this new enzyme, elucidating its mode of action and the chemical and structural characteristics that determine its rare specificity. "" All these synchronized steps were decisive, not only because they allowed us to know a little more about the fundamental physiology of these environmental mycobacteria but also because they provided Nuno Empadinhas adds that more effective antimycobacterial strategies than those currently available may be appropriate for the future development of more effective antimycobacterial strategies ". "This is a clear example of how the coordinated efforts of the different teams involved resulted in a result that was not accessible to any of them individually: a unique and detailed molecular map of this important biological process, which not only a starting point for our work

The study was mainly funded by the Foundation for Science and Technology, along with other supports – namely the North American2020 and Centro2020 programs.