Developing a Technological Platform to Create Innovative TB Drugs Active against Multidrug-Resistant Strains

摘要

In assessing the threats related to the 12 most dangerous infectious diseases, the World Health Organization (WHO) considers the struggle against multidrug-resistant/extensively drug-resistant (MDR/XDR) forms of the causative agent of tuberculosis, Mycobacterium tuberculosis, as the most crucial problem. The number of cases associated with MDR/XDR TB forms is constantly growing both across the world and in Russia (despite achievements in the reduction of tuberculosis mortality). The deterioration of the population's immune status because of the spread of HIV, hepatitis, type-2 diabetes, depression, and other factors, in particular, the intensification of migration processes, worsens the situation. The solution proposed in this article implies a complex interdisciplinary approach, including the development of, first, diagnostic kits based on fundamentally new technologies, which will make it possible to identify the entire spectrum of genes responsible for the development of drug resistance, as well as epidemiologically dangerous mutant lineages of tuberculosis under both clinical and field conditions, ensuring control over the real epidemiological situation in specific regions of Russia; second, antibiotics with a new action mechanism, active against MDR/XDR strains of the causative agent, including virulence inhibitors; third, genetically engineered vaccines, the development of which will account for the existing negative international experience and new scientific approaches, including those proposed in Russia; and, fourth, a new class of adjuvants for vaccines based on the Russian collection of probiotic strains of lactobacilli and bifidobacteria with selective immunomodulatory properties. Supposedly, these objectives will be implemented by the MDR/XDR TB consortium, which unites the best specialists-geneticists, microbiologists, immunologists, specialists in bioinformatics, medical chemists, and clinicians from 15 institutes of four departments (the Ministry of Science and Higher Education of the Russian Federation, the Ministry of Health of the Russian Federation, the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being (Rospotrebnadzor), and the Federal Biomedical Agency).