Cell Chemical Biology, volume 28, issue 10, pages 1420-1432.e9
A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases
Tkachenko Alexander G.
1, 2
,
Kashevarova Natalya M
2
,
Sidorov Roman Yu
1, 2
,
Nesterova Larisa Yu.
1, 2
,
Akhova Anna V.
1, 2
,
Tsyganov Ivan V
1, 2
,
Vaganov Vladimir Yu
1
,
Shipilovskikh Sergei A
,
Rubtsov Aleksandr E
,
Publication type: Journal Article
Publication date: 2021-10-01
Journal:
Cell Chemical Biology
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 8.6
ISSN: 24519448, 24519456
Drug Discovery
Biochemistry
Molecular Biology
Pharmacology
Clinical Biochemistry
Molecular Medicine
Abstract
Bacterial persistence coupled with biofilm formation is directly associated with failure of antibiotic treatment of tuberculosis. We have now identified 4-(4,7-DiMethyl-1,2,3,4-tetrahydroNaphthalene-1-yl)Pentanoic acid (DMNP), a synthetic diterpene analogue, as a lead compound that was capable of suppressing persistence and eradicating biofilms in Mycobacterium smegmatis. By using two reciprocal experimental approaches - ΔrelMsm and ΔrelZ gene knockout mutations versus relMsm and relZ overexpression technique - we showed that both RelMsm and RelZ (p)ppGpp synthetases are plausible candidates for serving as targets for DMNP. In vitro, DMNP inhibited (p)ppGpp-synthesizing activity of purified RelMsm in a concentration-dependent manner. These findings, supplemented by molecular docking simulation, suggest that DMNP targets the structural sites shared by RelMsm, RelZ, and presumably by a few others as yet unidentified (p)ppGpp producers, thereby inhibiting persister cell formation and eradicating biofilms. Therefore, DMNP may serve as a promising lead for development of antimycobacterial drugs.
Citations by journals
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2
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BIO Web of Conferences
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1 publication, 5.56%
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Synfacts
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1 publication, 5.56%
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Vavilovskii Zhurnal Genetiki i Selektsii (Vavilov Journal of Genetics and Breeding)
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1 publication, 5.56%
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1 publication, 5.56%
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1 publication, 5.56%
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1
2
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Citations by publishers
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1
2
3
4
5
6
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Multidisciplinary Digital Publishing Institute (MDPI)
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6 publications, 33.33%
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EDP Sciences
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2 publications, 11.11%
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2 publications, 11.11%
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1 publication, 5.56%
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Hindawi Limited
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1 publication, 5.56%
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Pleiades Publishing
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Pleiades Publishing
1 publication, 5.56%
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Thieme
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Thieme
1 publication, 5.56%
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Institute of Cytology and Genetics SB RAS
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Institute of Cytology and Genetics SB RAS
1 publication, 5.56%
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Springer Nature
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Springer Nature
1 publication, 5.56%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 5.56%
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1
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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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Tkachenko A. G. et al. A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases // Cell Chemical Biology. 2021. Vol. 28. No. 10. p. 1420-1432.e9.
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Tkachenko A. G., Kashevarova N. M., Sidorov R. Yu., Nesterova L. Y., Akhova A. V., Tsyganov I. V., Vaganov V. Yu., Shipilovskikh S. A., Shipilovskikh S. A., Rubtsov A. E., Rubtsov A. E., Malkov A. V. A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases // Cell Chemical Biology. 2021. Vol. 28. No. 10. p. 1420-1432.e9.
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TY - JOUR
DO - 10.1016/j.chembiol.2021.01.018
UR - https://doi.org/10.1016%2Fj.chembiol.2021.01.018
TI - A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases
T2 - Cell Chemical Biology
AU - Tkachenko, Alexander G.
AU - Kashevarova, Natalya M
AU - Sidorov, Roman Yu
AU - Nesterova, Larisa Yu.
AU - Akhova, Anna V.
AU - Tsyganov, Ivan V
AU - Vaganov, Vladimir Yu
AU - Shipilovskikh, Sergei A
AU - Rubtsov, Aleksandr E
AU - Malkov, A. V.
AU - Shipilovskikh, Sergei A
AU - Rubtsov, Aleksandr E
PY - 2021
DA - 2021/10/01 00:00:00
PB - Elsevier
SP - 1420-1432.e9
IS - 10
VL - 28
SN - 2451-9448
SN - 2451-9456
ER -
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@article{2021_Tkachenko,
author = {Alexander G. Tkachenko and Natalya M Kashevarova and Roman Yu Sidorov and Larisa Yu. Nesterova and Anna V. Akhova and Ivan V Tsyganov and Vladimir Yu Vaganov and Sergei A Shipilovskikh and Aleksandr E Rubtsov and A. V. Malkov and Sergei A Shipilovskikh and Aleksandr E Rubtsov},
title = {A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases},
journal = {Cell Chemical Biology},
year = {2021},
volume = {28},
publisher = {Elsevier},
month = {oct},
url = {https://doi.org/10.1016%2Fj.chembiol.2021.01.018},
number = {10},
pages = {1420--1432.e9},
doi = {10.1016/j.chembiol.2021.01.018}
}
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Tkachenko, Alexander G., et al. “A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases.” Cell Chemical Biology, vol. 28, no. 10, Oct. 2021, pp. 1420-1432.e9. https://doi.org/10.1016%2Fj.chembiol.2021.01.018.