Transcriptomics

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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. 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.

ORGANISM(S): Mycobacterium tuberculosis  

SUBMITTER: Benjamin K Johnson   Christopher J Colvin  Robert B. Abramovitch  Robert B Abramovitch 

PROVIDER: E-GEOD-63917 | ArrayExpress | 2015-05-20

SECONDARY ACCESSION(S): GSE63917SRP050863PRJNA269492

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

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

Johnson Benjamin K BK   Colvin Christopher J CJ   Needle David B DB   Mba Medie Felix F   Champion Patricia A DiGiuseppe PA   Abramovitch Robert B RB  

Antimicrobial agents and chemotherapy 20150518 8


Mycobacterium tuberculosis must sense and adapt to host environmental cues to establish and maintain an infection. The two-component regulatory system PhoPR plays a central role in sensing and responding to acidic pH within the macrophage and is required for M. tuberculosis intracellular replication and growth in vivo. Therefore, the isolation of compounds that inhibit PhoPR-dependent adaptation may identify new antivirulence therapies to treat tuberculosis. Here, we report that the carbonic anh  ...[more]

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