Protein Kinase B (PknB) of Mycobacterium tuberculosis is essential for growth of the pathogen in vitro as well as for survival within the host [Microbiology]

April 4th, 2014 by Chawla, Y., Upadhyay, S. K., Khan, S., Nagarajan, S. N., Forti, F., Nandicoori, V. K.

The Mycobacterium tuberculosis protein kinase B (PknB) comprises an intracellular kinase domain, connected through a transmembrane domain to an extracellular region that contains four PASTA domains. The present study describes the comprehensive analysis of different domains of PknB in the context of viability in avirulent and virulent mycobacteria. We find stringent regulation of PknB expression necessary for cell survival, with depletion or overexpression of PknB leading to cell death. While PknB-mediated kinase activity is essential for cell survival, active kinase lacking the transmembrane or extracellular domain fails to complement conditional mutants not expressing PknB. By creating chimeric kinases, we find that the intracellular kinase domain has unique functions in the virulent strain, which cannot be substituted by other kinases. Interestingly, we find that although the presence of the carboxy-terminal PASTA domain is dispensable in the avirulent M. smegmatis, all four PASTA domains are essential in M. tuberculosis. The differential behavior of PknB vis-a-vis the number of essential PASTA domains, and the specificity of kinase domain functions, suggests that PknB-mediated growth and signaling events differ in virulent compared to avirulent mycobacteria. Mouse infection studies were performed to determine the role of PknB in mediating pathogen survival in the host demonstrate that PknB is not only critical for growth of the pathogen in vitro, but is also essential for the survival of the pathogen in the host.
  • Posted in Journal of Biological Chemistry, Publications
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