Tuberculosis ranks 13th among the leading causes of death in the world, it is also the second most significant deadly infectious agent after COVID-19. However, fighting the mycobacteria that cause tuberculosis is not that simple: they infect alveolar macrophages, which for bacteria act as a kind of "shelter". The development of Russian scientists from Moscow State University is even more important: they created the antioxidant and antibiotic SkQ1, which allows to destroy mycobacteria not only in a free form, but also inside macrophages. The work is supported by a grant from the Russian Science Foundation and published in the journal Pharmaceuticals.
Usually, foreign objects absorbed by a macrophage are destroyed using lysosomes, but mycobacteria have the ability to evade being "digested" by the lysosome's enzymes. Thus, they bypass the body's immune response. Moreover, mycobacteria disrupt the restoration of macrophage cell membranes, which is why they lose their protective abilities.
In a joint work of scientists from the Belozersky Institute of Physico-Chemical Biology of Moscow University and the Central Tuberculosis Research Institute, it was shown that the previously developed SkQ1 mitochondrially-targeted antioxidant and antibiotic is effective not only against gram-negative and gram-positive bacteria, but also against Mycobacterium tuberculosis, the agent that causes tuberculosis in humans.
"Using compounds that disrupt bacterial bioenergy is a very effective tool for combating bacterial infections," said Pavel Nazarov, a senior researcher at the Department of Bioenergetics of the Institute of Physico-Chemical Biology at Moscow University.
"The ability of human cells to exist in the form of tissues, and the separation of energy processes and the transport of substances within a eukaryotic cell protects them from the action of SkQ1. However, individual cells that do not form tissues and are weakened by mycobacteria are not able to protect the mycobacterium from the antibiotic, which determines the success of the antibacterial action of SkQ1 in relation to mycobacteria" summed up Pavel Nazarov.