Open Access
Antibiotics, volume 10, issue 1, pages 6
Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis
Frolova Svetlana G
1, 2
,
Klimina Ksenia M.
1, 3
,
Kumar Ravinder
4
,
Vatlin Aleksey A
1, 5
,
Salunke Deepak B
4, 6
,
Kendrekar Pravinkumar
7
,
Danilenko Valery N.
1
,
Maslov Dmitry A
1
7
Unit for Drug Discovery Research (UDDR), Department of Health Sciences, Central University of Technology, Bloemfontein 9300, South Africa
|
Publication type: Journal Article
Publication date: 2020-12-23
PubMed ID:
33374765
Biochemistry
Microbiology (medical)
Microbiology
Infectious Diseases
Pharmacology (medical)
General Pharmacology, Toxicology and Pharmaceutics
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global burden, responsible for over 1 million deaths annually. The emergence and spread of drug-resistant M. tuberculosis strains (MDR-, XDR- and TDR-TB) is the main challenge in global TB-control, requiring the development of novel drugs acting on new biotargets, thus able to overcome the drug-resistance. Tryptanthrin is a natural alkaloid, with great therapeutic potential due to its simple way of synthesis and wide spectrum of biological activities including high bactericidal activity on both drug-susceptible and MDR M. tuberculosis strains. InhA was suggested as the target of tryptanthrins by in silico modeling, making it a promising alternative to isoniazid, able to overcome drug resistance provided by katG mutations. However, neither the mechanism of action of tryptanthrin nor the mechanism of resistance to tryptanthrins was ever confirmed in vitro. We show that the MmpS5-MmpL5 efflux system is able to provide resistance to tryptanthrins using an in-house test-system. Comparative genomic analysis of spontaneous tryptanthrin-resistant M. smegmatis mutants showed that mutations in MSMEG_1963 (EmbR transcriptional regulator) lead to a high-level resistance, while those in MSMEG_5597 (TetR transcriptional regulator) to a low-level one. Mutations in an MFS transporter gene (MSMEG_4427) were also observed, which might be involved in providing a basal level of tryptanthrins-resistance.
Citations by journals
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1
2
3
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Pharmaceuticals
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Pharmaceuticals
3 publications, 42.86%
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Biomedicines
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Biomedicines
1 publication, 14.29%
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Frontiers in Microbiology
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Frontiers in Microbiology
1 publication, 14.29%
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Russian Journal of Genetics
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Russian Journal of Genetics
1 publication, 14.29%
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RSC Medicinal Chemistry
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RSC Medicinal Chemistry
1 publication, 14.29%
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1
2
3
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Citations by publishers
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1
2
3
4
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
4 publications, 57.14%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 14.29%
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Pleiades Publishing
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Pleiades Publishing
1 publication, 14.29%
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Royal Society of Chemistry (RSC)
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Royal Society of Chemistry (RSC)
1 publication, 14.29%
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1
2
3
4
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Frolova S. G. et al. Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis // Antibiotics. 2020. Vol. 10. No. 1. p. 6.
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Frolova S. G., Klimina K. M., Kumar R., Vatlin A. A., Salunke D. B., Kendrekar P., Danilenko V. N., Maslov D. A. Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis // Antibiotics. 2020. Vol. 10. No. 1. p. 6.
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RIS
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TY - JOUR
DO - 10.3390/antibiotics10010006
UR - https://doi.org/10.3390%2Fantibiotics10010006
TI - Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis
T2 - Antibiotics
AU - Frolova, Svetlana G
AU - Klimina, Ksenia M.
AU - Kumar, Ravinder
AU - Vatlin, Aleksey A
AU - Salunke, Deepak B
AU - Danilenko, Valery N.
AU - Kendrekar, Pravinkumar
AU - Maslov, Dmitry A
PY - 2020
DA - 2020/12/23 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 6
IS - 1
VL - 10
PMID - 33374765
SN - 2079-6382
ER -
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@article{2020_Frolova,
author = {Svetlana G Frolova and Ksenia M. Klimina and Ravinder Kumar and Aleksey A Vatlin and Deepak B Salunke and Valery N. Danilenko and Pravinkumar Kendrekar and Dmitry A Maslov},
title = {Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis},
journal = {Antibiotics},
year = {2020},
volume = {10},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {dec},
url = {https://doi.org/10.3390%2Fantibiotics10010006},
number = {1},
pages = {6},
doi = {10.3390/antibiotics10010006}
}
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MLA
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Frolova, Svetlana G., et al. “Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis.” Antibiotics, vol. 10, no. 1, Dec. 2020, p. 6. https://doi.org/10.3390%2Fantibiotics10010006.