Studying the mechanism of action of new derivatives of quinoxalin-1,4-dioxide on the model organism Mycobacterium smegmatis
- Authors: Vatlin A.A.1,2, Frolova S.G.1, Bekker O.B.1, Danilenko V.N.1
-
Affiliations:
- Vavilov Institute of General Genetics, Russian Academy of Sciences
- RUDN University
- Issue: Vol 32, No 1 (2024)
- Pages: 41-50
- Section: Industrial Ecology
- URL: https://journal-vniispk.ru/2313-2310/article/view/324094
- DOI: https://doi.org/10.22363/2313-2310-2024-32-1-41-50
- EDN: https://elibrary.ru/GWENSS
- ID: 324094
Cite item
Abstract
According to the World Health Organization (WHO), antibiotic resistance is currently one of the most serious threats to human health, food security, and development. Tuberculosis (TB) remains one of the deadliest bacterial diseases. The primary challenge in treating tuberculosis infection is the emergence of strains with multidrug resistance (MDR) to 4-9 drugs. The emergence of bacterial strains with MDR is a consequence of patients’ insufficient adherence to treatment, interrupted therapy, improperly prescribed courses of chemotherapy, and, according to recent data, the accumulation of antibiotics in the environment, which can activate the natural drug resistance system in bacteria. The consequences of MDR to antibiotics include prolonged hospitalizations, increased medical expenses, and mortality. Therefore, the task is to develop new effective antibacterial agents with novel mechanisms to reduce the emergence of bacterial resistance. In this study, we investigated the mechanisms of action of new promising antimycobacterial derivatives of quinoxalin-1,4-dioxide on the model organism Mycobacterium smegmatis .
Keywords
About the authors
Aleksey A. Vatlin
Vavilov Institute of General Genetics, Russian Academy of Sciences; RUDN University
Author for correspondence.
Email: vatlin_alexey123@mail.ru
ORCID iD: 0000-0002-6673-7633
Candidate of Biological Sciences, Senior Researcher, Laboratory of Microorganism Genetics
3 Gubkin St, Moscow, 119333, Russian FederationSvetlana G. Frolova
Vavilov Institute of General Genetics, Russian Academy of Sciences
Email: sveta.frolova.1997@bk.ru
Junior Researcher, Laboratory of Microorganism Genetics, Institute of General Genetics 3 Gubkin St, Moscow, 119333, Russian Federation
Olga B. Bekker
Vavilov Institute of General Genetics, Russian Academy of Sciences
Email: obbekker@mail.ru
Candidate of Biological Sciences, Senior Researcher Laboratory of Microorganism Genetics, Institute of General Genetics 3 Gubkin St, Moscow, 119333, Russian Federation
Valeriy N. Danilenko
Vavilov Institute of General Genetics, Russian Academy of Sciences
Email: valerid@vigg.ru
Doctor of Biological Sciences, Professor, Head of the Laboratory of Microorganism Genetics 3 Gubkin St, Moscow, 119333, Russian Federation
References
- Salari N, Kanjoori AH, Hosseinian-Far A, Hasheminezhad R, Mansouri K, Mohammadi M. Global prevalence of drug-resistant tuberculosis: a systematic review and meta-analysis. Infectious Diseases of Poverty. 2023 May 25;12(1):57. http://doi.org/10.1186/s40249-023-01107-x
- Tiberi S, Utjesanovic N, Galvin J, Centis R, D’Ambrosio L, van den Boom M, et al. Drug resistant TB - latest developments in epidemiology, diagnostics and management. Int Journal Infection Diseases. 2022 Nov;124 Suppl 1:S20-5.
- Prieto Martin Gil S, Tajuelo A, López-Siles M, McConnell MJ. Subinhibitory Concentrations of Clinically-Relevant Antimicrobials Affect Resistance-Nodulation-Division Family Promoter Activity in Acinetobacter baumannii. Frontiers in Microbiology. 2021;12.
- Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathogens. 2011 Jul;7(7):e1002158.
- Stanton IC, Murray AK, Zhang L, Snape J, Gaze WH. Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration. Communication Biology. 2020 Sep 3;3(1):1-11.
- Frolova SG, Vatlin AA, Maslov DA, Yusuf B, Buravchenko GI, Bekker OB, et al. Novel Derivatives of Quinoxaline-2-carboxylic Acid 1,4-Dioxides as Antimycobacterial Agents: Mechanistic Studies and Therapeutic Potential. Pharmaceuticals. 2023 Nov;16(11):1565.
- Junnotula V, Sarkar U, Sinha S, Gates KS. Initiation of DNA strand cleavage by 1,2,4-benzotriazine 1,4-dioxide antitumor agents: mechanistic insight from studies of 3-methyl-1,2,4-benzotriazine 1,4-dioxide. Journal American Chemical Society. 2009 Jan 28;131(3):1015-24.
- Snapper SB, Melton RE, Mustafa S, Kieser T, Jr WRJ. Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Molecular Microbiology. 1990;4(11):1911-9.
- Buravchenko GI, Maslov DA, Alam MS, Grammatikova NE, Frolova SG, Vatlin AA, et al. Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents. Pharmaceuticals. 2022 Feb;15(2):155.
- Lázaro-Silva DN, Mattos JCPD, Castro HC, Alves GG, Amorim LMF. The Use of DNA Extraction for Molecular Biology and Biotechnology Training: A Practical and Alternative Approach. Creative Education. 2015 May 19;6(8):762-72.
- Parish T, Brown AC (eds.). Mycobacteria Protocols: Second Edition. In: Methods in Molecular Biology. Totowa, NJ: Humana Press; 2009. Vol. 465.
- Erkmen O. Practice 18 - Antibiotic sensitivity test technique. In: O Erkmen (ed.). Academic Press; Laboratory Practices in Microbiology; 2021. p. 181-186.
- Blokpoel MCJ, Murphy HN, O’Toole R, Wiles S, Runn ESC, Stewart GR, et al. Tetracycline-inducible gene regulation in mycobacteria. Nucleic Acids Researches. 2005 Feb 1;33(2):e22.
Supplementary files
