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A signature protein of Mycobacterium tuberculosis (Rv000) modulates the transcriptome of Mycobacterium smegmatis.

ABSTRACT: The world’s second deadliest disease tuberculosis is caused by the organism Mycobacterium tuberculosis. Mtb has 4173 genes (Mycobrowser) and some of these genes are essential for its survival. There are many uncharacterized genes in Mtb which play an important role in its survival strategies to combat the immune system of the host. In order to identify vital genes required for its survival were characterized by in silico approach. Based on computational analysis, we have identified 2 proteins which are only present in Mtb complex and named as Signature Protein 1 & 2. The Signature protein 2 (Rv000) has DNA methyltransferase activity and also protects the DNA from DNase-I digestion. Knock in of this gene in Mycobacterium smegmatis modulates its transcriptome and thereby enhances the survival. RNA seq analysis of M. smegmatis showed that more than 3000 genes were up regulated at the transcriptional level. These results suggested that the gene encoding signature protein 2 (Rv000) is acting as a global transcriptional regulators. These genes encode proteins that belong to different categories of biological and molecular function i.e. transcriptional regulators, regulatory proteins, conserved hypothetical proteins, transporter proteins (ABC transporters, antiporter, sugar transporter and Major facilitator superfamily genes) and TonB dependent receptors (required for iron scavenging) were upregulated. The proteins encoded by these genes may be targeted for drug development against Mtb..

ORGANISM(S): Mycolicibacterium smegmatis

PROVIDER: GSE126837 | GEO | 2021/06/13

REPOSITORIES: GEO

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Project description:The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria: Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC = Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis

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A signature protein of Mycobacterium tuberculosis (Rv000) modulates the transcriptome of Mycobacterium smegmatis.

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