SCIENTIFIC EDUCATIONAL CENTER science idea

Scientists from the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences, Peoples' Friendship University of Russia and South Ural State University, together with colleagues from the University of the Western Cape Province (South Africa), have proposed drugs that block bacterial pump proteins that can literally throw medicine out of the cell. Although these substances themselves are not antibiotics, they will help defeat the resistance of pathogenic microorganisms to existing antibiotics. In particular, the study makes a significant contribution to the development of drugs against drug-resistant strains of tuberculosis.
The fight against tuberculosis is complicated by the fact that uncontrolled use of antibiotics contributes to the spread of drug-resistant strains of the causative agent of tuberculosis.
"One of the biochemical mechanisms that ensure the development of antibiotic resistance is the removal of the drug from the bacterial cell. Specific membrane proteins are responsible for this-pumps or efflux pumps that literally emit molecules dangerous to the pathogen of the disease. They can become a target for an effective fight against drug resistance," says Dmitry Maslov, the project manager for the RNF grant, senior researcher at the Laboratory of Microbial Genetics of IOGen RAS.
In the current work, protein pumps of the non—pathogenic Mycobacterium Mycobacterium smegmatis, a close relative of tuberculosis pathogens, were investigated. The MmpS5-MmpL5 efflux system of this microorganism is capable of pumping out the main anti-tuberculosis drugs. Using molecular modeling methods, scientists have created a model of it and identified drugs suitable for blocking it from the ASINEX database of antibacterial compounds. Out of a hundred potential inhibitors, five best ones were selected, which can be well excreted from the body, and are also safe for animal cells. A series of in vitro experiments on mycobacteria confirmed the effectiveness of two compounds predicted by a theoretical 3D model and computational calculations.
"We expect that based on the results obtained, it will be possible to improve the created model and select more such molecules from the Gold & PlatinumASINEX databases. In the future, they will be tested directly on Mycobacterium tuberculosis. The results of our research will be used in the development of new effective drugs that can help existing anti-tuberculosis drugs, such as bedaquiline, overcome drug resistance of tuberculosis due to efflux," Dmitry Maslov sums up.
The works were carried out with the financial support of the Russian Science Foundation (RNF).
The article was published in the journal Biomedicines
PHOTO: Paper mugs are impregnated with an antibiotic (3a) and efflux pump inhibitors; they were placed on a medium with seeded microorganisms. The identified drugs themselves do not destroy mycobacteria, but enhance the effect of the antibiotic © Dmitry Maslov
Source: polit.ru , sci-dig.ru