Journal
SCIENCE ADVANCES
Volume 7, Issue 26, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abg2517
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Funding
- Sweden-America Foundation
- NIH/NIAID [R01 AI109044, R21 AI138550]
- NIH [1S10 OD020062-01]
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This study reveals that the intracellular bacterial pathogen Rickettsia parkeri uses two protein-lysine methyltransferases (PKMTs) to modify outer membrane proteins (OMPs) and prevent their ubiquitylation, thus evading autophagic targeting. Lysine methylation is shown to be an essential determinant of rickettsial pathogenesis by shielding bacterial proteins from ubiquitylation.
Many intracellular pathogens avoid detection by their host cells. However, it remains unknown how they avoid being tagged by ubiquitin, an initial step leading to antimicrobial autophagy. Here, we show that the intracellular bacterial pathogen Rickettsia parkeri uses two protein-lysine methyltransferases (PKMTs) to modify outer membrane proteins (OMPs) and prevent their ubiquitylation. Mutants deficient in the PKMTs were avirulent in mice and failed to grow in macrophages because of ubiquitylation and autophagic targeting. Lysine methylation protected the abundant surface protein OmpB from ubiquitin-dependent depletion from the bacterial surface. Analysis of the lysine-methylome revealed that PKMTs modify a subset of OMPs, including OmpB, by methylation at the same sites that are modified by host ubiquitin. These findings show that lysine methylation is an essential determinant of rickettsial pathogenesis that shields bacterial proteins from ubiquitylation to evade autophagic targeting.
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