@entity2497 BCG response regulator essential for XXXX dormancy.

@entity7913 @entity26 @entity519 @entity378 @entity2497
Obligately aerobic tubercle bacilli are capable of adapting to survive @entity519 by developing into a nonreplicating or dormant form. Dormant bacilli maintain viability for extended periods. Furthermore, they are resistant to antimycobacterials, and hence, dormancy might play a role in the persistence of @entity378 infection despite prolonged chemotherapy. Previously, we have grown dormant @entity2497 BCG in an @entity26 -limited Wayne culture system and subjected the bacilli to proteome analysis. This work revealed the upregulation of the response regulator Rv3133c and three other polypeptides (alpha-crystallin and two "conserved hypothetical" proteins) upon entry into dormancy. Here, we replaced the coding sequence of the response regulator with a @entity7913 resistance cassette and demonstrated that the loss-of-function mutant died after @entity26 starvation-induced termination of growth. Thus, the disruption of this dormancy-induced transcription factor resulted in loss of the ability of BCG to adapt to survival of @entity519 . Two-dimensional gel electrophoresis of protein extracts from the gene-disrupted strain showed that the genetic loss of the response regulator caused loss of the induction of the other three dormancy proteins. Thus, the upregulation of these dormancy proteins requires the response regulator. Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator. Our results provide conclusive evidence that DosR is a key regulator in the @entity26 starvation-induced mycobacterial dormancy response.
