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Title: Evolutionary conserved mutations in PhoPR attenuate the virulence of animal-adapted tuberculosis strains for humans      
dateReleased:
07-07-2014
description:
By genome comparison of 30 MTBC strains, we identified three SNPs affecting the phoPR genes of members of the animal and M. africanum lineages that were not seen in the M. tuberculosis sensu-stricto genomes. The genes phoPR encode a two component regulatory system that is known for its strong impact on virulence and immunogenicity of M. tuberculosis due to its key role in the regulation of genes involved in lipid synthesis and secretion of the 6 kDa secreted antigenic target ESAT-6. To explore whether these SNPs affect the expression of the PhoP regulon, we compared the transcriptome of M. tuberculosis mutants lacking the endogenous phoPR genes (ΔphoPR) and their complemented derivatives expressing either the M. bovis or M. tuberculosis allele of phoPR (phoPR-bovis and phoPR-TB respectively). These comparisons were performed in parallel in two M. tuberculosis strains from distinct genetic backgrounds, i.e. strain GC1237 from lineage 2 (also named East-Asia or Beijing cluster) and the H37Rv reference strain from lineage 4 (also named Euro-American cluster). To perform the transcriptomic comparison of the different M. tuberculosis variants (ΔphoPR, complemented and wt) from the two distinct genetic background, a customized micro-array has been designed then manufactured by Agilent (8 x 15k format). The design of oligonucleotides covering all protein coding sequences was done using OligoArray version 2.1 on the basis of the 3924 predicted coding sequences composing the entire M. tuberculosis H37Rv reference genome. The experimental data for each of the comparison consisted of 4 hybridizations (2 biological replicates with dye-swap); 16 in the end for each genetic background.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-54421
refinement:
raw
alternateIdentifiers:
54421
keywords:
functional genomics
dateModified:
07-15-2014
availability:
available
types:
gene expression
name:
Mycobacterium tuberculosis
ID:
A-GEOD-18222
name:
Agilent-025942 Mycobacterium tuberculosis H37rv_oligoDB 024084
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54421/E-GEOD-54421.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54421/E-GEOD-54421.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54421
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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