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Journal of Bacteriology, July 2009, p. 4546-4554, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00245-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Survival of Pathogenic Mycobacteria in Macrophages Is Mediated through Autophosphorylation of Protein Kinase G{triangledown} ,{dagger}

Nicole Scherr,{ddagger} Philipp Müller,{ddagger} Damir Perisa, Benoît Combaluzier, Paul Jenö, and Jean Pieters*

Biozentrum, University of Basel, Basel, Switzerland

Received 23 February 2009/ Accepted 9 May 2009

Pathogenic mycobacteria survive within macrophages through the inhibition of phagosome-lysosome fusion. A crucial factor for avoiding lysosomal degradation is the mycobacterial serine/threonine protein kinase G (PknG). PknG is released into the macrophage cytosol upon mycobacterial infection, suggesting that PknG might exert its activity by interfering with host signaling cascades, but the mode of action of PknG remains unknown. Here, we show that PknG undergoes autophosphorylation on threonine residues located at the N terminus. In contrast to all other mycobacterial kinases investigated thus far, autophosphorylation of PknG was not involved in the regulation of its kinase activity. However, autophosphorylation was crucial for the capacity of PknG to promote mycobacterial survival within macrophages. These results will contribute to a better understanding of the virulence mechanisms of pathogenic mycobacteria and may help to design improved inhibitors of PknG to be developed as antimycobacterial compounds.


* Corresponding author. Mailing address: Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland. Phone: 41 61 267 14 94. Fax: 41 61 267 21 48. E-mail: jean.pieters{at}unibas.ch

{triangledown} Published ahead of print on 15 May 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} N.S. and P.M. contributed equally to this work.


Journal of Bacteriology, July 2009, p. 4546-4554, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00245-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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