Protein kinase G from pathogenic mycobacteria promotes survival within macrophages.
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.
Walburger
Anne
A
Biozentrum, University of Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
Koul
Anil
A
Ferrari
Giorgio
G
Nguyen
Liem
L
Prescianotto-Baschong
Cristina
C
Huygen
Kris
K
Klebl
Bert
B
Thompson
Charles
C
Bacher
Gerald
G
Pieters
Jean
J
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D008247:Lysosomes / Q000382:microbiology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D051379:Mice; D009163:Mycobacterium bovis / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development* / Q000472:pathogenicity; D020102:Mycobacterium smegmatis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity; D010588:Phagosomes / Q000201:enzymology / Q000382:microbiology* / Q000502:physiology; D015398:Signal Transduction; D013876:Thiophenes / Q000494:pharmacology; D014617:Vacuoles / Q000382:microbiology
C487783:AX 20017; D000577:Amides; D004791:Enzyme Inhibitors; D013876:Thiophenes; D017869:Cyclic GMP-Dependent Protein Kinases