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The carbonic anhydrase inhibitor ethoxzolamide inhibits the Mycobacterium tuberculosis PhoPR regulon and Esx-1 secretion and attenuates virulence

ABSTRACT: The purpose of this study was to examine how ethoxzolamide modulates gene M. tuberculosis gene expression at acidic pH. We observed that ethoxzolamide downregulates genes of the PhoPR regulon.

ORGANISM(S): Mycobacterium tuberculosis

PROVIDER: GSE63917 | GEO | 2015/05/20

SECONDARY ACCESSION(S): PRJNA269492

REPOSITORIES: GEO

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The carbonic anhydrase inhibitor ethoxzolamide inhibits the Mycobacterium tuberculosis PhoPR regulon and Esx-1 secretion and attenuates virulence

Project description:The purpose of this study was to examine how ethoxzolamide modulates gene M. tuberculosis gene expression at acidic pH. We observed that ethoxzolamide downregulates genes of the PhoPR regulon. Mtb strain CDC1551 was grown at 37C in T-25 vented, standing tissue culture flasks in 8 ml of buffered 7H9 medium seeded an initial OD of 0.2. Three conditions were examined with two biological replicates: 1) DMSO treated, pH 7.0, 2) DMSO treated, pH 5.7, 3) 40 µM ethoxzolamide treated, pH 5.7. The CDC1551(phoP::Tn) mutant was grown in a similar manner and treated with DMSO at pH 7.0 and 5.7. Following six days incubation, total bacterial RNA was extracted and analyzed as previously described.

2015-05-20 | E-GEOD-63917 | biostudies-arrayexpress

The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence.

Project description: Not available

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Mycobacterium avium subsp. paratuberculosis K-10 & phoPR comparison

Project description:To compare the transcriptional profile of K-10 and phoPR in the log phase, and to find out the effects of phoPR on MAP gene expression.

2016-03-01 | GSE71291 | GEO

Mycobacterium avium subsp. paratuberculosis K-10 & phoPR comparison

Project description:To compare the transcriptional profile of K-10 and phoPR in the log phase, and to find out the effects of phoPR on MAP gene expression. There are three replicates from K-10 as the control samples, and three replicates from phoPR used to examine the differences.

2016-03-01 | E-GEOD-71291 | biostudies-arrayexpress

Evolutionary conserved mutations in PhoPR attenuate the virulence of animal-adapted tuberculosis strains for humans

2014-07-07 | GSE54421 | GEO

Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

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Evolutionary conserved mutations in PhoPR attenuate the virulence of animal-adapted tuberculosis strains for humans

Project 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 (M-NM-^TphoPR) 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 (M-NM-^TphoPR, 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.

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carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

Project description:cea05-01_carbonic-anhydrase - carbonic anhydrase (1 or 2) simple or double mutants - Identification of genes differentially expressed in leaves of single CA1 and CA2 T-DNA insertional mutants and in the corresponding double mutant vs wild type - CA1 (At3g01500) and CA2 (At5g14740) T-DNA insertional mutant lines, the double (CA1+CA2) mutant and wild type Arabidopsis seeds were sown in soil in a phytotron. Leaves were harvested 40 days later for RNA extraction 6 dye-swap - gene knock out

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carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

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