Open Access
Pathogens, volume 9, issue 3, pages 166
MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines
Publication type: Journal Article
Publication date: 2020-02-28
PubMed ID:
32121069
Molecular Biology
Microbiology (medical)
Infectious Diseases
General Immunology and Microbiology
Immunology and Allergy
Abstract
The emergence and spread of drug-resistant Mycobacterium tuberculosis strains (including MDR, XDR, and TDR) force scientists worldwide to search for new anti-tuberculosis drugs. We have previously reported a number of imidazo[1,2-b][1,2,4,5]tetrazines–putative inhibitors of mycobacterial eukaryotic-type serine-threonine protein-kinases, active against M. tuberculosis. Whole genomic sequences of spontaneous drug-resistant M. smegmatis mutants revealed four genes possibly involved in imidazo[1,2-b][1,2,4,5]tetrazines resistance; however, the exact mechanism of resistance remain unknown. We used different approaches (construction of targeted mutants, overexpression of the wild-type (w.t.) and mutant genes, and gene-expression studies) to assess the role of the previously identified mutations. We show that mutations in MSMEG_1380 gene lead to overexpression of the mmpS5-mmpL5 operon in M. smegmatis, thus providing resistance to imidazo[1,2-b][1,2,4,5]tetrazines by increased efflux through the MmpS5-MmpL5 system, similarly to the mechanisms of resistance described for M. tuberculosis and M. abscessus. Mycobacterial MmpS5-MmpL5 transporters should be considered as an MDR-efflux system and they should be taken into account at early stages of anti-tuberculosis drug development.
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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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Maslov D. A. et al. MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines // Pathogens. 2020. Vol. 9. No. 3. p. 166.
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Maslov D. A., Shur K. V., Vatlin A. A., Danilenko V. N. MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines // Pathogens. 2020. Vol. 9. No. 3. p. 166.
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TY - JOUR
DO - 10.3390/pathogens9030166
UR - https://doi.org/10.3390%2Fpathogens9030166
TI - MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines
T2 - Pathogens
AU - Maslov, Dmitry A
AU - Shur, Kirill V
AU - Vatlin, Aleksey A
AU - Danilenko, Valery N.
PY - 2020
DA - 2020/02/28 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 166
IS - 3
VL - 9
PMID - 32121069
SN - 2076-0817
ER -
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@article{2020_Maslov,
author = {Dmitry A Maslov and Kirill V Shur and Aleksey A Vatlin and Valery N. Danilenko},
title = {MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines},
journal = {Pathogens},
year = {2020},
volume = {9},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {feb},
url = {https://doi.org/10.3390%2Fpathogens9030166},
number = {3},
pages = {166},
doi = {10.3390/pathogens9030166}
}
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Maslov, Dmitry A., et al. “MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines.” Pathogens, vol. 9, no. 3, Feb. 2020, p. 166. https://doi.org/10.3390%2Fpathogens9030166.