Aureolic Acid Group of Agents as Potential Antituberculosis Drugs
<i>Mycobacterium tuberculosis</i> is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work...
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doaj-bcbac0f8dad14f068a5853452365adff2020-11-25T03:59:40ZengMDPI AGAntibiotics2079-63822020-10-01971571510.3390/antibiotics9100715Aureolic Acid Group of Agents as Potential Antituberculosis DrugsJulia Bespyatykh0Dmitry Bespiatykh1Maja Malakhova2Ksenia Klimina3Andrey Bespyatykh4Anna Varizhuk5Anna Tevyashova6Tatiana Nikolenko7Galina Pozmogova8Elena Ilina9Egor Shitikov10Federal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaGause Institute of New Antibiotics, 199021 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, RussiaFederal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, Russia<i>Mycobacterium tuberculosis</i> is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, antibiotics of the aureolic acid group were tested on a model organism <i>Mycobacterium smegmatis</i>. We presumed that antibiotics of this group may be potential G4 ligands. However, this was not confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed morphological changes in the cell structure upon treatment. Transcriptomic analysis documented increased expression of <i>MSMEG_3743/soj</i> and <i>MSMEG_4228/ftsW</i>, involved in cell division. Therefore, drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a septum. Additionally, a decrease in the transcription level of several indispensable genes, such as nitrate reductase subunits (<i>MSMEG_5137/narI</i> and <i>MSMEG_5139/narX</i>) and <i>MSMEG_3205/hisD</i> was shown. We concluded that the mechanism of action of aureolic acid and its related compounds may be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs.https://www.mdpi.com/2079-6382/9/10/715<i>Mycobacterium smegmatis</i>TB treatmentOlivomycin<i>Mycobacterium tuberculosis</i>transcriptomic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Bespyatykh Dmitry Bespiatykh Maja Malakhova Ksenia Klimina Andrey Bespyatykh Anna Varizhuk Anna Tevyashova Tatiana Nikolenko Galina Pozmogova Elena Ilina Egor Shitikov |
spellingShingle |
Julia Bespyatykh Dmitry Bespiatykh Maja Malakhova Ksenia Klimina Andrey Bespyatykh Anna Varizhuk Anna Tevyashova Tatiana Nikolenko Galina Pozmogova Elena Ilina Egor Shitikov Aureolic Acid Group of Agents as Potential Antituberculosis Drugs Antibiotics <i>Mycobacterium smegmatis</i> TB treatment Olivomycin <i>Mycobacterium tuberculosis</i> transcriptomic |
author_facet |
Julia Bespyatykh Dmitry Bespiatykh Maja Malakhova Ksenia Klimina Andrey Bespyatykh Anna Varizhuk Anna Tevyashova Tatiana Nikolenko Galina Pozmogova Elena Ilina Egor Shitikov |
author_sort |
Julia Bespyatykh |
title |
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs |
title_short |
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs |
title_full |
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs |
title_fullStr |
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs |
title_full_unstemmed |
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs |
title_sort |
aureolic acid group of agents as potential antituberculosis drugs |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2020-10-01 |
description |
<i>Mycobacterium tuberculosis</i> is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, antibiotics of the aureolic acid group were tested on a model organism <i>Mycobacterium smegmatis</i>. We presumed that antibiotics of this group may be potential G4 ligands. However, this was not confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed morphological changes in the cell structure upon treatment. Transcriptomic analysis documented increased expression of <i>MSMEG_3743/soj</i> and <i>MSMEG_4228/ftsW</i>, involved in cell division. Therefore, drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a septum. Additionally, a decrease in the transcription level of several indispensable genes, such as nitrate reductase subunits (<i>MSMEG_5137/narI</i> and <i>MSMEG_5139/narX</i>) and <i>MSMEG_3205/hisD</i> was shown. We concluded that the mechanism of action of aureolic acid and its related compounds may be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs. |
topic |
<i>Mycobacterium smegmatis</i> TB treatment Olivomycin <i>Mycobacterium tuberculosis</i> transcriptomic |
url |
https://www.mdpi.com/2079-6382/9/10/715 |
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