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Science 304 (5678): 1800-1804

Copyright © 2004 by the American Association for the Advancement of Science

Protein Kinase G from Pathogenic Mycobacteria Promotes Survival Within Macrophages

Anne Walburger,1* Anil Koul,2* Giorgio Ferrari,1* Liem Nguyen,1* Cristina Prescianotto-Baschong,1 Kris Huygen,3 Bert Klebl,2 Charles Thompson,1 Gerald Bacher,2 Jean Pieters1{dagger}

Abstract: Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages, allowing them to survive intracellularly. We found that the eukaryotic-like serine/threonine protein kinase G from pathogenic mycobacteria was secreted within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating intracellular survival of mycobacteria. Inactivation of protein kinase G by gene disruption or chemical inhibition resulted in lysosomal localization and mycobacterial cell death in infected macrophages. Besides identifying a target for the control of mycobacterial infections, these findings suggest that pathogenic mycobacteria have evolved eukaryotic-like signal transduction mechanisms capable of modulating host cell trafficking pathways.

1 Biozentrum, University of Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
2 Axxima Pharmaceuticals AG, Max-Lebsche-Platz 32, 81377 Munich, Germany.
3 Pasteur Institute, Engelandstraat 642, B1180 Brussels, Belgium.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jean.pieters{at}unibas.ch

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