Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

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...

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Bibliographic Details
Published in:Antibiotics (Basel) 2020-10, Vol.9 (10), p.715
Main Authors: Bespyatykh, Julia, Bespiatykh, Dmitry, Malakhova, Maja, Klimina, Ksenia, Bespyatykh, Andrey, Varizhuk, Anna, Tevyashova, Anna, Nikolenko, Tatiana, Pozmogova, Galina, Ilina, Elena, Shitikov, Egor
Format: Article
Language:English
Subjects:
Acids
Analysis
Antibiotics
Antiinfectives and antibacterials
Antimicrobial activity
Antineoplastic agents
Antitubercular agents
Cell division
Cytology
Drug discovery
Drug dosages
Drug resistance
Drug therapy
Drugs
Environmental aspects
Forecasts and trends
Genes
Genomes
Ligands
Methods
Mycobacterium smegmatis
Mycobacterium tuberculosis
NAD
NADH
Nicotinamide adenine dinucleotide
Nitrate reductase
Olivomycin
Reductases
Septum
TB treatment
Transcription
transcriptomic
Tuberculosis
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Summary: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 . 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 and , 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 ( and ) and 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.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics9100715