Downregulation of protein kinase C-alpha enhances intracellular survival of Mycobacteria: role of PknG.
BACKGROUND
Intracellular trafficking of mycobacteria is comprehensively dependent on the unusual regulation of host proteins. Recently, we have reported that infection of macrophages by Mycobacterium tuberculosis H37Rv (Rv) selectively downregulates the expression of PKCalpha while infection by Mycobacterium smegmatis (MS) does not.


RESULTS
Based on our earlier study, we have extrapolated for the first time that knockdown of PKCalpha, impairs phagocytosis of mycobacteria by macrophages while their intracellular survival is drastically increased. Mycobacterium bovis BCG (BCG) and Mycobacterium tuberculosis H37Ra (Ra) have also been shown to downregulate the expression of PKCalpha during the infection. Since PknG is uniquely expressed in BCG, Ra, Rv but not in MS and has been reported to promote intracellular survival of mycobacteria, led us to believe that PknG may be involved in such downregulation of PKCalpha. THP-1 cells infected with recombinant MS expressing PknG (MS-G), showed significant reduction in PKCalpha expression. In normal THP-1 cells survival of MS-G was enhanced as compared to MS, while their behavior in PKCalpha deficient cells could not be distinguished. The results strongly demonstrate that pathogenic mycobacteria recognize and then inhibit PKCalpha to circumvent phagocytosis and the hostile environment of macrophages. We emphasize that, this inhibition is controlled by PknG.


CONCLUSIONS
All together, our data reveal a mechanism that shows substantial interdependence of PKCalpha with PknG, in sustaining mycobacterial infection.
Chaurasiya
Shivendra K
SK
Division of Microbiology, Central Drug Research Institute, Lucknow, 226001, India. shivendrachaurasiya@gmail.com
Srivastava
Kishore K
KK
D002460:Cell Line; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D003600:Cytosol / Q000382:microbiology; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D050296:Microbial Viability; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D020102:Mycobacterium smegmatis / Q000276:immunology / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors*; D037521:Virulence Factors / Q000502:physiology*
D037521:Virulence Factors; D017869:Cyclic GMP-Dependent Protein Kinases; D051571:Protein Kinase C-alpha