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Omics score: 42

Complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis

ABSTRACT: Using a deletion mutant lacking portions of the response regulator, MprA, and the histidine kinase, MprB, we demonstrated by DNA microarrays that MprAB activates sigE and sigB under SDS stress and during logarithmic growth. Keywords: effects of 0.05% SDS on Mtb gene expression Overall design: The expression of SigE-regulated genes {Manganelli, 2004 #212} was evaluated in SDS-treated and control cultures of H37Rv and Rv-D981, using array analyses, for each pair of samples in each experiment, dye flips were performed

INSTRUMENT(S): PHRI-UMNDJ Mycobacterium tuberculosis 4.8K CAG_Mtb

SUBMITTER: Saleena Ghanny

PROVIDER: GSE6750 | GEO | 2007-03-28

SECONDARY ACCESSION(S): PRJNA98953

REPOSITORIES: GEO

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Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis.

Pang Xiuhua X Vu Phong P Byrd Thomas F TF Ghanny Saleena S Soteropoulos Patricia P Mukamolova Galina V GV Wu Shiping S Samten Buka B Howard Susan T ST

Microbiology (Reading, England) 20070401 Pt 4

Two-component systems are important constituents of bacterial regulatory networks. Results of this investigation into the role of the MprAB two-component system of Mycobacterium tuberculosis indicate that it is associated with the regulation of several stress-responsive regulons. Using a deletion mutant lacking portions of the response regulator, MprA, and the histidine kinase, MprB, it was demonstrated by real-time PCR, primer extension analyses and DNA microarrays that MprAB activates sigma fa ...[more]

PMID: 17379732

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MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis.

Project description:The genetic mechanisms mediating the adaptation of Mycobacterium tuberculosis within the host are poorly understood. The best-characterized regulatory systems in this organism include sigma factors and two-component signal transduction systems. mprAB is a two-component system required by M. tuberculosis for growth in vivo during the persistent stage of infection. In this report, we demonstrate that MprAB is stress responsive and regulates the expression of numerous stress-responsive genes in M. tuberculosis. With DNA microarrays and quantitative real-time reverse transcription-PCR, genes regulated by MprA in M. tuberculosis that included two stress-responsive sigma factors were identified. Response regulator MprA bound to conserved motifs in the upstream regions of both sigB and sigE in vitro and regulated the in vivo expression of sigB and sigE in M. tuberculosis. In addition, mprA itself was induced following exposure to stress, establishing a direct role for this regulatory system in stress response pathways of M. tuberculosis. Induction of mprA and sigE by MprA in response to stress was mediated through the cognate sensor kinase MprB and required expression of the extracytoplasmic loop domain. These results provide the first evidence that recognition of and adaptation to specific stress in M. tuberculosis are mediated through activation of a two-component signal transduction system that directly regulates the expression of stress-responsive determinants.

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Project description:Coordinated regulation of molecular chaperones is an important feature of the bacterial stress response. The small molecular chaperone gene acr2 of Mycobacterium tuberculosis is activated by exposure to several stresses, including heat and the detergent sodium dodecyl sulfate (SDS). In this study, we show that acr2 is directly regulated by the MprAB two-component system, and that MprAB has both positive and negative effects on acr2 expression. mRNA analyses showed that acr2 expression levels were lower under SDS stress and control conditions but higher under heat shock in an mprAB deletion mutant than they were in the parental strain. Parental expression patterns were restored in an mprAB-complemented strain. Western blotting using an anti-Acr2 antibody showed that Acr2 protein synthesis correlated with mRNA levels. Primer extension identified one transcriptional start point (TSP) for acr2 in all three strains under control and stress conditions. Electrophoresis mobility shift assays revealed multiple MprA binding sites in the acr2 promoter, including one downstream and three upstream of the acr2 TSP, with one overlapping the binding sites predicted for SigE, SigH, and HspR. DNA footprinting confirmed that MprA protected large sections of the acr2 promoter region. Expression of several housekeeping genes under SDS stress also was evaluated, revealing the upregulation of large molecular chaperone genes and, unexpectedly, sigA, with slightly lower sigA mRNA levels detected in the mprAB deletion mutant than in the wild type. In contrast to Acr2, SigA protein synthesis did not correlate with mRNA expression. Overall, the data indicated that MprA has complex interactions with the acr2 promoter and indirect effects on major housekeeping genes.

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