MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J Bacteriol 2006 Mar;188(6):2134-43
Date
03/04/2006Pubmed ID
16513743Pubmed Central ID
PMC1428128DOI
10.1128/JB.188.6.2134-2143.2006Scopus ID
2-s2.0-33644857465 (requires institutional sign-in at Scopus site) 130 CitationsAbstract
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.
Author List
He H, Hovey R, Kane J, Singh V, Zahrt TCMESH terms used to index this publication - Major topics in bold
Adaptation, PhysiologicalBacterial Proteins
Base Sequence
DNA, Bacterial
Electrophoretic Mobility Shift Assay
Gene Expression Profiling
Gene Expression Regulation, Bacterial
Genes, Bacterial
Heat-Shock Proteins
Molecular Sequence Data
Mycobacterium tuberculosis
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Protein Binding
Protein Kinases
RNA, Bacterial
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Sigma Factor
Signal Transduction
