Role of HrcA in stress management in Mycobacterium tuberculosis

The current study aims to understand the role of HrcA in stress response of M. tuberculosis.

In this study, using an hrcA knock out mutant of M. tuberculosis it is demonstrated that the heat shock repressor, HrcA is important for countering environmental stresses pathogen faces within the host during the infection process. Also, with scanning electron microscopy, it has been shown that HrcA plays a role in maintaining the morphology and cell size of the pathogen as disruption of the hrcA gene resulted in significantly elongated bacilli. Furthermore, heat shock proteins like ClpC1, ClpB, DnaK, GroEL2, GroEL1, DnaJ2 and GroES were detected in the secretome of M. tuberculosis by mass spectrometric analysis. The study also demonstrates a strong humoral response against M. tuberculosis heat shock proteins in H₃₇ R_v -infected mice sera.

The study establishes that though hrcA is not an essential gene for M. tuberculosis, it regulates the expression of heat shock proteins during infection and disruption of hrcA gives a survival advantage to the pathogen during stress conditions.

HrcA plays an important role in maintaining a fine balance of heat shock proteins during infection to give adequate survival advantage and also evade immune detection.