Computational genomics-proteomics and Phylogeny analysis of twenty one mycobacterial genomes (Tuberculosis &amp; non Tuberculosis strains)

Zakham, Fathiah; Aouane, Othmane; Ussery, David W.; Benjouad, Abdelaziz; Ennaji, Moulay Mustapha

doi:10.1186/2042-5783-2-7

Cited by 28 publications

(26 citation statements)

References 46 publications

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“…Also, the number of proteins shared by Mbov and Mtb, with Map (atypical mycobacteria) was less than the proteins shared between Mbov and Mtb. This was similar to the earlier reports based on 16S rRNA based phylogenetic study 34 . During pair-wise comparison of conserved proteins among the four species of Yersinia, Ype and Yps shared maximum number of proteins.…”

Section: Discussionsupporting

confidence: 93%

Comparative in-silico proteomic analysis discerns potential granuloma proteins of Yersinia pseudotuberculosis

Aswal

Garg

Singhal

et al. 2020

Sci Rep

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Yersinia pseudotuberculosis is one of the three pathogenic species of the genus Yersinia. Most studies regarding pathogenesis of Y. pseudotuberculosis are based on the proteins related to type iii secretion system, which is a well-known primary virulence factor in pathogenic Gram-negative bacteria, including Y. pseudotuberculosis. information related to the factors involved in Y. pseudotuberculosis granuloma formation is scarce. in the present study we have used a computational approach to identify proteins that might be potentially involved in formation of Y. pseudotuberculosis granuloma. A comparative proteome analysis and conserved orthologous protein identification was performed between two different genera of bacteria-Mycobacterium and Yersinia, their only common pathogenic trait being ability to form necrotizing granuloma. comprehensive analysis of orthologous proteins was performed in proteomes of seven bacterial species. this included M. tuberculosis, M. bovis and M. avium paratuberculosis-the known granuloma forming Mycobacterium species, Y. pestis and Y. frederiksenii-the non-granuloma forming Yersinia species and, Y. enterocolitica-that forms micro-granuloma and, Y. pseudotuberculosis-a prominent granuloma forming Yersinia species. In silico proteome analysis indicated that seven proteins (UniProt id A0A0U1QT64, A0A0U1QTE0, A0A0U1QWK3, A0A0U1R1R0, A0A0U1R1Z2, A0A0U1R2S7, A7FMD4) might play some role in Y. pseudotuberculosis granuloma. Validation of the probable involvement of the seven proposed Y. pseudotuberculosis granuloma proteins was done using transcriptome data analysis and, by mapping on a composite protein-protein interaction map of experimentally proved M. tuberculosis granuloma proteins (RD1 locus proteins, ESAT-6 secretion system proteins and intra-macrophage secreted proteins). Though, additional experiments involving knocking out of each of these seven proteins are required to confirm their role in Y. pseudotuberculosis granuloma our study can serve as a basis for further studies on Y. pseudotuberculosis granuloma. The genus Yersinia is comprised of Gram-negative, catalase-positive, facultative anaerobic enteric-bacteria. Though, the optimal temperature for growth is 28 °C, some members of the genus can survive at low temperatures ca. 4 °C 1. Most species of the genus Yersinia grow extracellularly, except Y. pseudotuberculosis and Y. pestis which are capable of intracellular growth, i.e. inside the host macrophages 2. Of the sixteen known species of Yersinia, only three are pathogenic Y. pestis, Y. pseudotuberculosis and Y. enterocolitica 3,4. In humans, infection with Y. pestis results in plague, while infection with Y. pseudotuberculosis and Y. enterocolitica results in gastroenteritis, which is usually self-limiting 5. Besides man, Y. pseudotuberculosis can infect a wide range of animals including swines, dogs, rodents, birds etc. 6-9. Y. pseudotuberculosis infection in animals can lead to tuberculosis-like symptoms, including localized tissue necrosis and granulomas in the liver, sple...

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Section: Discussionsupporting

confidence: 93%

Comparative in-silico proteomic analysis discerns potential granuloma proteins of Yersinia pseudotuberculosis

Aswal

Garg

Singhal

et al. 2020

Sci Rep

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“…Thus, on the basis of promoter and terminator motifs we conclude that this RNA attenuator is only present in a subset of pathogenic mycobacteria with a phylogenetic split between MBTC/ M. marinum/M. ulcerans and M. leprae, which is consistent with the split seen by aligning 16S sequences (37). Moreover, only M. tuberculosis, M. bovis and M. avium appear to have a functional antisense promoter, indicating that the presumably tight regulation provided by multiple promoters, RNA attenuator and asRNA is specific for species within the MTBC.…”

Section: Resultssupporting

confidence: 79%

Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis

Schwenk

Moores

Nobeli³

et al. 2017

Preprint

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The success of Mycobacterium tuberculosis as a pathogen relies on the ability to switch between active growth and non-replicating persistence, associated with latent TB infection. Resuscitation promoting factors (Rpfs) are essential for the transition of M. tuberculosis to dormancy and for emergence from the non-replicating persistent state. But these enzymes are double-edged swords, as their ability to degrade the cell wall, is potentially lethal to the bacterium itself. Hence, Rpf expression is tightly regulated. We have identified a novel regulatory element in the 5’ untranslated region (UTR) of rpfB. We demonstrate that this element is a transcriptionally regulated RNA switch/riboswitch candidate, which is restricted to pathogenic mycobacteria, suggesting a role in virulence. Moreover, we have used translation start site mapping to re-annotate the RpfB start codon and identified and validated a ribosome binding site that is likely to be targeted by an RpfB antisense RNA. Finally, we show that rpfB is co-transcribed with downstream genes, ksgA and ispE. ksgA encodes a universally conserved methyl transferase involved in ribosome maturation and ispE encodes an essential ATP-dependent kinase involved in cell wall synthesis. This arrangement implies co-regulation of resuscitation, cell wall synthesis and ribosome maturation via the RNA switch. We propose that deregulation of this switch, associated with cell wall synthesis and ribosome function, presents a new target for anti-tuberculosis drug development.ImportanceThis work describes the identification and characterisation of a novel regulatory RNA element/attenuator that controls cell wall synthesis and ribosome function in Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB). By switching between two different conformations, this RNA switch can either enable or inhibit transcription of a tri-cistronic mRNA that encodes a cell-wall remodelling enzyme crucial for activation of latent TB, an RNA methytransferase that is important for ribosome function and a protein kinase essential for early steps in cell wall synthesis. This RNA switch is only present in a subset of pathogenic mycobacteria, and by regulating the expression of three genes associated with classical antimicrobial targets we believe that it offers a novel important target for future anti-tuberculosis drugs.

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“…All four subspecies are virtually identical at the genomic level (7,8). Likewise, species within the M. tuberculosis complex are all highly similar based on genomic and proteomic comparisons (9). However, these two mycobacterial complexes are more distantly related to each other and are easily distinguishable.…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array

Bannantine

Campo

Randall

et al. 2017

Clin Vaccine Immunol

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Johne's disease, a chronic gastrointestinal inflammatory disease caused by Mycobacterium avium subspecies paratuberculosis, is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. Given the close phylogenetic relationship between M. avium subsp. paratuberculosis and the human pathogen Mycobacterium tuberculosis, here, we applied a whole-proteome M. tuberculosis protein array to identify seroreactive and diagnostic M. avium subsp. paratuberculosis antigens. A genome-scale pairwise analysis of amino acid identity levels between orthologous proteins in M. avium subsp. paratuberculosis and M. tuberculosis showed an average of 62% identity, with more than half the orthologous proteins sharing Ͼ75% identity. Analysis of the M. tuberculosis protein array probed with sera from M. avium subsp. paratuberculosisinfected cattle showed antibody binding to 729 M. tuberculosis proteins, with 58% of them having Ն70% identity to M. avium subsp. paratuberculosis orthologs. The results showed that only 4 of the top 40 seroreactive M. tuberculosis antigens were orthologs of previously reported M. avium subsp. paratuberculosis antigens, revealing the existence of a large number of previously unrecognized candidate diagnostic antigens. Enzyme-linked immunosorbent assay (ELISA) testing of 20 M. avium subsp. paratuberculosis recombinant proteins, representing reactive and nonreactive M. tuberculosis orthologs, further confirmed that the M. tuberculosis array has utility as a screening tool for identifying candidate antigens for Johne's disease diagnostics. Additional ELISA testing of field serum samples collected from dairy herds around the United States revealed that MAP2942c had the strongest seroreactivity with Johne's disease-positive samples. Collectively, our studies have considerably expanded the number of candidate M. avium subsp. paratuberculosis proteins with potential utility in the next generation of rationally designed Johne's disease diagnostic assays.

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Computational genomics-proteomics and Phylogeny analysis of twenty one mycobacterial genomes (Tuberculosis & non Tuberculosis strains)

Cited by 28 publications

References 46 publications

Comparative in-silico proteomic analysis discerns potential granuloma proteins of Yersinia pseudotuberculosis

Comparative in-silico proteomic analysis discerns potential granuloma proteins of Yersinia pseudotuberculosis

Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis

Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array

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