The mystery of mycobacterial energy metabolism is revealed
Recently, I learned from Nankai University that the Chinese Academy of Sciences academician Rao Zi and his team have cooperated with many scientific research institutions at home and abroad to solve the mystery of energy metabolism of Mycobacterium tuberculosis, and to lay an important foundation for the research and development of new drugs against drug-resistant tuberculosis. Published in the international top academic journal Science.
Mycobacterium tuberculosis, a pathogen of tuberculosis, has shown increasing resistance in recent years, and multidrug-resistant tuberculosis and extreme drug-resistant tuberculosis have become major challenges to human health. Cutting off the energy supply line of pathogenic bacteria, making it "hunger-to-death" has become a new way to deal with drug-resistant tuberculosis.
Based on the high-resolution cryo-electron microscopy structure of the mycobacterial energy metabolism system respiratory chain super complex, Rao Zi and the team revealed a new electron transfer mechanism coupled with oxygen reduction and oxygen reduction in living organisms. At the same time, for the first time through structural biology research, it was found that superoxide dismutase (SOD) directly participates in the assembly of the respiratory chain system oxidoreductase super complex and works synergistically. Blocking of the respiratory chain super complex is an important strategy for the development of drugs to inhibit their expansion and infestation. “Super complexes are important for the energy supply of multiple pathogens under the actinomycetes of M. tuberculosis.†Rao Zihe said, “This complex of team research is a hot drug target and is currently in clinical II. The drug molecule Telacebec (Q203) blocks the aerobic respiration pathway of Mycobacterium tuberculosis by inhibiting the binding of the natural substrate of the complex, thereby exerting pharmacological effects. This study will greatly promote the development of similar or more effective new drugs for further optimization of drugs.
"For the first time, from the perspective of structural biology, it was confirmed that SOD has a direct interaction with the respiratory chain complex in the periplasm of mycobacteria, and has the effect of scavenging potential free radicals and synergistic redox reactions." According to members, more importantly, this finding suggests that this may be an important mechanism by which actinomycetes, represented by M. tuberculosis, resist host immune responses in host macrophages. This brings new insights to further understanding the interaction between M. tuberculosis and the host.
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