Unknown

Dataset Information

0

The MprB extracytoplasmic domain negatively regulates activation of the Mycobacterium tuberculosis MprAB two-component system.


ABSTRACT: Mycobacterium tuberculosis is an acid-fast pathogen of humans and the etiological agent of tuberculosis (TB). It is estimated that one-third of the world's population is latently (persistently) infected with M. tuberculosis. M. tuberculosis persistence is regulated, in part, by the MprAB two-component signal transduction system, which is activated by and mediates resistance to cell envelope stress. Here we identify MprAB as part of an evolutionarily conserved cell envelope stress response network and demonstrate that MprAB-mediated signal transduction is negatively regulated by the MprB extracytoplasmic domain (ECD). In particular, we report that deregulated production of the MprB sensor kinase, or of derivatives of this protein, negatively impacts M. tuberculosis growth. The observed growth attenuation is dependent on MprAB-mediated signal transduction and is exacerbated in strains of M. tuberculosis producing an MprB variant lacking its ECD. Interestingly, full-length MprB, and the ECD of MprB specifically, immunoprecipitates the Hsp70 chaperone DnaK in vivo, while overexpression of dnaK inhibits MprAB-mediated signal transduction in M. tuberculosis grown in the absence or presence of cell envelope stress. We propose that under nonstress conditions, or under conditions in which proteins present in the extracytoplasmic space are properly folded, signaling through the MprAB system is inhibited by the MprB ECD. Following exposure to cell envelope stress, proteins present in the extracytoplasmic space become unfolded or misfolded, leading to removal of the ECD-mediated negative regulation of MprB and subsequent activation of MprAB.

SUBMITTER: Bretl DJ 

PROVIDER: S-EPMC3911260 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2006-01-01 | S-EPMC1428128 | BioStudies
2003-01-01 | S-EPMC308901 | BioStudies
2010-01-01 | S-EPMC2832534 | BioStudies
2011-01-01 | S-EPMC3062566 | BioStudies
2015-01-01 | S-EPMC4642893 | BioStudies
2011-01-01 | S-EPMC3248964 | BioStudies
1000-01-01 | S-EPMC3418728 | BioStudies
2008-01-01 | S-EPMC2258413 | BioStudies
1000-01-01 | S-EPMC2519537 | BioStudies
2018-01-01 | S-EPMC7020242 | BioStudies