title: Survival of pathogenic mycobacteria in macrophages is mediated through autophosphorylation of protein kinase G.
abstract: 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.
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Scherr
authors.forename: Philipp
authors.initials: P
authors.lastname: Müller
authors.forename: Damir
authors.initials: D
authors.lastname: Perisa
authors.forename: Benoît
authors.initials: B
authors.lastname: Combaluzier
authors.forename: Paul
authors.initials: P
authors.lastname: Jenö
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology*; D050296:Microbial Viability; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation; D013912:Threonine / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D013912:Threonine; D017869:Cyclic GMP-Dependent Protein Kinases