The incidence of tuberculosis is decreasing, but those strains that survive and circulate are increasingly multidrug resistant. Thus, the development of new drugs remains critical. At the same time, it is desirable to understand the possible mechanism of mycobacterial resistance already at the initial stage of drug development.
On April 8, 2025, the scientific news portal PCR.NEWS published an article “Experimental evolution of the tuberculosis pathogen reveals potential mechanisms of resistance to new drugs". It describes a recent article coauthored by scientists from St. Petersburg Pasteur Institute. Journal Antibiotics (Basel) published an article by Russian and Bulgarian scientists about the in vitro study of the mechanisms of resistance of Mycobacterium tuberculosis to new compounds of different chemical classes. Spontaneous mutant clones were obtained that are resistant to increased concentrations of new derivatives of aroylhydrazones and nitrofuroylamides developed by Bulgarian co-authors.
Scientists have shown by in vitro experiments that Mycobacterium tuberculosis is able to quickly respond to potential anti-tuberculosis compounds that are only in the process of laboratory development. At the same time, mutations in different resistant clones affected various and unrelated genetic mechanisms mostly mediating the stress response and efflux pumps.
"The next direction of our research is the implementation of a long-term experiment to assess not only the primary reaction of the microbe within one month of cultivation, but possible changes over a long period of time," says Igor Mokrousov, head of laboratory of molecular epidemiology and evolutionary genetics.
Reference: Mokrousov I, Angelova VT, Slavchev I, Bezruchko MV, Dimitrov S, Polev DE, Dobrikov GM, Valcheva V. Genomic Insight into Primary Adaptation of Mycobacterium tuberculosis to Aroylhydrazones and Nitrofuroylamides In Vitro // Antibiotics (Basel). 2025; 14(3):225. doi: 10.3390/antibiotics14030225. https://www.mdpi.com/2079-6382/14/3/225