title: MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: He
authors.forename: Raymond
authors.initials: R
authors.lastname: Hovey
authors.forename: Jason
authors.initials: J
authors.lastname: Kane
authors.forename: Vineet
authors.initials: V
authors.lastname: Singh
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Zahrt
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012329:RNA, Bacterial / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012808:Sigma Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins; C480224:MprA protein, Mycobacterium tuberculosis; D012329:RNA, Bacterial; D012333:RNA, Messenger; C079011:SigB protein, Bacteria; D012808:Sigma Factor; C111259:sigE protein, Bacteria; D011494:Protein Kinases; C480223:MprB protein, Mycobacterium tuberculosis