A Quinoxaline 1,4-Dioxide Activates DNA Repair Systems in Mycobacterium smegmatis: A Transcriptomic Study
In 2022, the World Health Organization reported that tuberculosis (TB) was the second leading cause of death globally from a single infectious agent following COVID-19. The development of new antitubercular agents with novel mechanisms of action for use in complex TB therapy is considered a key approach to combating TB. In this study, we examined the gene expression profile of <i>M. smegmatis</i> when exposed to a promising antituberculosis agent, quinoxaline 1,4-dioxide (QdNO) 7-chloro-2-(ethoxycarbonyl)-3-methyl-6-(piperazin-1-yl)quinoxaline-1,4-dioxide-1 (LCTA-3368). We investigated how the bacterial response changed with different minimum inhibitory concentrations (MIC) (1/4 × MIC, 1/2 × MIC, and 1 × MIC) and durations (30 min and 90 min) of treatment with the drug. Our analysis revealed significant upregulation in genes involved in DNA repair and replication processes, as well as changes in the expression of 95 genes encoding proteins with oxidoreductase activity. We additionally showed that the concentration of reactive oxygen species increases in a dose-dependent manner upon exposure of <i>M. smegmatis</i> to LCTA-3368. These findings support the proposed mechanism of antibacterial action of QdNOs, which is associated with the formation of free radicals leading to DNA damage.
Authors
- Dmitry A. Maslov (ORCID: https://orcid.org/0000-0003-4296-5815)
- Vladimir A. Veselovsky (ORCID: https://orcid.org/0000-0002-4336-9452)
- В. Н. Даниленко (ORCID: https://orcid.org/0000-0001-5780-0621)
- Egor Shitikov (ORCID: https://orcid.org/0000-0002-4865-6004)
- Aleksey A. Vatlin (ORCID: https://orcid.org/0000-0002-6499-3908)
- Ksenia M. Klimina (ORCID: https://orcid.org/0000-0002-5563-644X)
- Svetlana G. Frolova
- Rustem Abuzarovich Ilyasov (ORCID: https://orcid.org/0000-0003-2445-4739)
- Olga B. Bekker (ORCID: https://orcid.org/0000-0003-2015-0025)
- Dmitry Bespiatykh (ORCID: https://orcid.org/0000-0003-0867-5988)
- N. I. Kochetkov (ORCID: https://orcid.org/0000-0002-2196-5421)
- Svetlana V. Smirnova (ORCID: https://orcid.org/0000-0002-8286-9345)
- Diana A. Reznikova (ORCID: https://orcid.org/0009-0003-3725-8101)
- Olesya O. Galanova (ORCID: https://orcid.org/0009-0001-3512-9571)
Institutions
- Peoples' Friendship University of Russia (RU)
- Koltzov Institute of Developmental Biology (RU)
- Moscow State University of Technologies and Management named after K.G. Razumovskiy (RU)
- Vavilov Institute of General Genetics (RU)
- Federal Medical-Biological Agency (RU)
- Stanford University (US)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-04-14
- DOI
- https://doi.org/10.3390/ijms26083689
- Primary Topic
- Synthesis and Biological Evaluation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Education and Science of the Russian Federation
- RUDN University