Computational insights into promoter architecture of toxin-antitoxin systems of Mycobacterium tuberculosis

Thakur, Zoozeal; Saini, Vandana; Arya, Preeti; Kumar, Ajit; Mehta, Promod K

doi:10.1016/j.gene.2017.10.054

Cited by 15 publications

(10 citation statements)

References 61 publications

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“…Gallinarum genomes indicates their possible role in growth regulation, niche adaptation, encountering of various stress responses inside macrophage as well as in persistence, as has been observed in various bacteria and archaea including S . Typhimurium LT2, [ 24 , 117 , 119 ]. Moreover, the biological significance of presence of large number of TA’s may be due to their potential involvement in number of underlying regulatory pathways, as can be inferred by identification of different domains such as GNATlike_domain (24 nos.…”

Section: Discussionmentioning

confidence: 99%

Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes

et al. 2021

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Salmonella enterica serovar Gallinarum biovar Pullorum (bvP) and biovar Gallinarum (bvG) are the etiological agents of pullorum disease (PD) and fowl typhoid (FT) respectively, which cause huge economic losses to poultry industry especially in developing countries including India. Vaccination and biosecurity measures are currently being employed to control and reduce the S. Gallinarum infections. High endemicity, poor implementation of hygiene and lack of effective vaccines pose challenges in prevention and control of disease in intensively maintained poultry flocks. Comparative genome analysis unravels similarities and dissimilarities thus facilitating identification of genomic features that aids in pathogenesis, niche adaptation and in tracing of evolutionary history. The present investigation was carried out to assess the genotypic differences amongst S.enterica serovar Gallinarum strains including Indian strain S. Gallinarum Sal40 VTCCBAA614. The comparative genome analysis revealed an open pan-genome consisting of 5091 coding sequence (CDS) with 3270 CDS belonging to core-genome, 1254 CDS to dispensable genome and strain specific genes i.e. singletons ranging from 3 to 102 amongst the analyzed strains. Moreover, the investigated strains exhibited diversity in genomic features such as virulence factors, genomic islands, prophage regions, toxin-antitoxin cassettes, and acquired antimicrobial resistance genes. Core genome identified in the study can give important leads in the direction of design of rapid and reliable diagnostics, and vaccine design for effective infection control as well as eradication. Additionally, the identified genetic differences among the S. enterica serovar Gallinarum strains could be used for bacterial typing, structure based inhibitor development by future experimental investigations on the data generated.

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Section: Discussionmentioning

confidence: 99%

Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes

et al. 2021

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“…RNA-seq experiments indicated a potential transcription start site (TSS) of mbcA in M. tuberculosis (indicated as +1 in Figure 4) and located 34 nucleotides upstream from its translation initiation site (TIS) [15]. Based on bioinformatics analysis, it has been proposed that transcription of the mbcAT operon occurs from two overlapping promoters recognized by RNA polymerase holoenzyme using alternative sigma factors [17]. An upstream promoter, with a σ L -dependent -10 element (GGTTC) located at position -54 to -50 from the TIS, and a second promoter, using a σ H -dependent -10 element (CGTGTC), located at positions -50 to -45.…”

Section: Discussionmentioning

confidence: 99%

Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System

Ariyachaokun

Grabowska

Gutierrez

2020

Toxins

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MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD+ and its bactericidal activity is neutralized by physical interaction with its cognate antitoxin MbcA. Therefore, the MbcTA system appears as a promising target for the development of novel therapies against tuberculosis, through the identification of compounds able to antagonize or destabilize the MbcA antitoxin. Here, the expression of the mbcAT operon and its regulation were investigated. A dual fluorescent reporter system was developed, based on an integrative mycobacterial plasmid that encodes a constitutively expressed reporter, serving as an internal standard for monitoring mycobacterial gene expression, and an additional reporter, dependent on the promoter under investigation. This system was used both in M. tuberculosis and in the fast growing model species Mycobacterium smegmatis to: (i) assess the autoregulation of mbcAT; (ii) perform a genetic dissection of the mbcA promoter/operator region; and (iii) explore the regulation of mbcAT transcription from the mbcA promoter (PmbcA) in a variety of stress conditions, including in vivo in mice and in macrophages.

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“…One person may be infected by TB when only inhaling a few of TB germs. So, many scientists studied the characteristics including codon usage pattern [ 2 ], promoter architecture of toxin-antitoxin systems [ 3 ], drug-resistance [ 4 ], molecular epidemiology [ 5 ], protein function and immunogenicity [ 6 ], and drugs for the treatment [ 7 ] of TB. Typically, Sheen et al studied the multiple genomes of Mycobacterium tuberculosis and found out some specific novel genes and mutations associated with pyrazinamide resistance [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis and Comparison on the Codon Usage Pattern of Whole Mycobacterium tuberculosis Coding Genome from Different Area

Ren

Haixian

et al. 2018

BioMed Research International

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Phenomenon of unequal use of synonymous codons in Mycobacterium tuberculosis is common. Codon usage bias not only plays an important regulatory role at the level of gene expression, but also helps in improving the accuracy and efficiency of translation. Meanwhile, codon usage pattern of Mycobacterium tuberculosis genome is important for interpreting evolutionary characteristics in species. In order to investigate the codon usage pattern of the Mycobacterium tuberculosis genome, 12 Mycobacterium tuberculosis genomes from different area are downloaded from the GeneBank. The correlations between G3, GC12, whole GC content, codon adaptation index, codon bias index, and so on of Mycobacterium tuberculosis genomes are calculated. The ENC-plot, relationship between A3/(A3 + T3) and G3/(G3 + C3), GC12 versus GC3 plot, and the RSCU of overall/separated genomes all show that the codon usage bias exists in all 12 Mycobacterium tuberculosis genomes. Lastly, relationship between CBI and the equalization of ENC shows a strong negative correlation between them. The relationship between protein length and GC content (GC3 and GC12) shows that more obvious differences in the GC content may be in shorter protein. These results show that codon usage bias existing in the Mycobacterium tuberculosis genomes could be used for further study on their evolutionary phenomenon.

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Computational insights into promoter architecture of toxin-antitoxin systems of Mycobacterium tuberculosis

Cited by 15 publications

References 61 publications

Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes

Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes

Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System

Comprehensive Analysis and Comparison on the Codon Usage Pattern of Whole Mycobacterium tuberculosis Coding Genome from Different Area

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