title: Protein kinase G from pathogenic mycobacteria promotes survival within macrophages.
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.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Walburger
authors.forename: Anil
authors.initials: A
authors.lastname: Koul
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ferrari
authors.forename: Liem
authors.initials: L
authors.lastname: Nguyen
authors.forename: Cristina
authors.initials: C
authors.lastname: Prescianotto-Baschong
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Bert
authors.initials: B
authors.lastname: Klebl
authors.forename: Charles
authors.initials: C
authors.lastname: Thompson
authors.forename: Gerald
authors.initials: G
authors.lastname: Bacher
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
mesh_terms: 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
chemical_list: C487783:AX 20017; D000577:Amides; D004791:Enzyme Inhibitors; D013876:Thiophenes; D017869:Cyclic GMP-Dependent Protein Kinases