System OMICs analysis of Mycobacterium tuberculosis Beijing B0/W148 cluster

Bespyatykh, Julia; Shitikov, Egor; Guliaev, Andrei; Smolyakov, Alexander; Klimina, Ksenia M.; Veselovsky, Vladimir A.; Malakhova, M V; Arapidi, Georgij; Dogonadze, Marine; Manicheva, Olga; Bespiatykh, Dmitry; Mokrousov, Igor; Zhuravlev, Viacheslav; Ilina, Elena N.; Govorun, Vadim M.

doi:10.1038/s41598-019-55896-z

Cited by 8 publications

(7 citation statements)

References 43 publications

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“…According to phylogenetic analysis and drug susceptibility tests, strains 267/47 and 120/26 demonstrated a high level of resistance similar to other members of the clusters. Moreover, the strains were closely clustered to the previously studied strains RUS_B0 [ 32 ] and Rostov [ 21 ] ( Figures S1 and S2 ). Both M. tuberculosis clinical strains were slow-growing compared to the control strain H37Rv ( Figure 1 ).…”

Section: Discussionsupporting

confidence: 64%

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MDR and Pre-XDR Clinical Mycobacterium tuberculosis Beijing Strains: Assessment of Virulence and Host Cytokine Response in Mice Infectious Model

et al. 2021

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Mycobacterium tuberculosis Beijing genotype associated with drug resistance is a growing public health problem worldwide. The aim of this study was the assessment of virulence for C57BL/6 mice after infection by clinical M. tuberculosis strains 267/47 and 120/26, which belong to the modern sublineages B0/W148 and Central Asia outbreak of the Beijing genotype, respectively. The sublineages were identified by the analysis of the strains’ whole-genomes. The strains 267/47 and 120/26 were characterized as agents of pre-extensively drug-resistant (pre-XDR) and multidrug-resistant (MDR) tuberculosis, respectively. Both clinical strains were slow-growing in 7H9 broth compared to the M. tuberculosis H37Rv strain. The survival rates of C57BL/6 mice infected by 267/47, 120/26, and H37Rv on the 150th day postinfection were 10%, 40%, and 70%, respectively. Mycobacterial load in the lungs, spleen, and liver was higher and histopathological changes were more expressed for mice infected by the 267/47 strain compared to those infected by the 120/26 and H37Rv strains. The cytokine response in the lungs of C57BL/6 mice after infection with the 267/47, 120/26, and H37Rv strains was different. Notably, proinflammatory cytokine genes Il-1α, Il-6, Il-7, and Il-17, as well as anti-inflammatory genes Il-6 and Il-13, were downregulated after an infection caused by the 267/47 strain compared to those after infection with the H37Rv strain.

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Section: Discussionsupporting

confidence: 64%

“…The tree was visualized with the ggtree v.2.0.2 [ 30 ] package for R v.4.0.2 [ 31 ]. WGS data for CAO and Beijing B0/W148 clusters were taken from our previous studies [ 11 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

MDR and Pre-XDR Clinical Mycobacterium tuberculosis Beijing Strains: Assessment of Virulence and Host Cytokine Response in Mice Infectious Model

et al. 2021

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“…DNase treatment was carried out as previously described ( Bespyatykh et al, 2019 ) with TURBO DNA-free kit (Thermo Fisher Scientific, Waltham, MA, United States), in volumes of 100 μl, and further with the RNase-Free DNase Set (Qiagen, Hilden, Germany), according to the manufacturers’ protocol. RNA cleanup was performed with the RNeasy Mini Kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic Profile of Mycobacterium smegmatis in Response to an Imidazo[1,2-b][1,2,4,5]tetrazine Reveals Its Possible Impact on Iron Metabolism

et al. 2021

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Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex bacteria, is one of the most pressing health problems. The development of new drugs and new therapeutic regimens effective against the pathogen is one of the greatest challenges in the way of tuberculosis control. Imidazo[1,2-b][1,2,4,5]tetrazines have shown promising activity against M. tuberculosis and M. smegmatis strains. Mutations in MSMEG_1380 lead to mmpS5–mmpL5 operon overexpression, which provides M. smegmatis with efflux-mediated resistance to imidazo[1,2-b][1,2,4,5]tetrazines, but the exact mechanism of action of these compounds remains unknown. To assess the mode of action of imidazo[1,2-b][1,2,4,5]tetrazines, we analyzed the transcriptomic response of M. smegmatis to three different concentrations of 3a compound: 1/8×, 1/4×, and 1/2× MIC. Six groups of genes responsible for siderophore synthesis and transport were upregulated in a dose-dependent manner, while virtual docking revealed proteins involved in siderophore synthesis as possible targets for 3a. Thus, we suggest that imidazo[1,2-b][1,2,4,5]tetrazines may affect mycobacterial iron metabolism.

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“…Total RNA was isolated from all M. smegmatis cultures, as previously described [ 45 , 46 ]. DNase treatment was carried out with TURBO DNA-free kit (Thermo Fisher Scientific, Waltham, MA, USA), in volumes of 100 µL, and further with the RNase-Free DNase Set (Qiagen, Hilden, Germany), according to the manufacturers’ protocol.…”

Section: Methodsmentioning

confidence: 99%

Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

et al. 2020

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Mycobacterium tuberculosis 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 Mycobacterium smegmatis. 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 MSMEG_3743/soj and MSMEG_4228/ftsW, 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 (MSMEG_5137/narI and MSMEG_5139/narX) and MSMEG_3205/hisD 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.

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System OMICs analysis of Mycobacterium tuberculosis Beijing B0/W148 cluster

Cited by 8 publications

References 43 publications

MDR and Pre-XDR Clinical Mycobacterium tuberculosis Beijing Strains: Assessment of Virulence and Host Cytokine Response in Mice Infectious Model

MDR and Pre-XDR Clinical Mycobacterium tuberculosis Beijing Strains: Assessment of Virulence and Host Cytokine Response in Mice Infectious Model

Transcriptomic Profile of Mycobacterium smegmatis in Response to an Imidazo[1,2-b][1,2,4,5]tetrazine Reveals Its Possible Impact on Iron Metabolism

Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

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