SIK2 orchestrates actin-dependent host response upon Salmonella infection

Proc Natl Acad Sci U S A. 2021 May 11;118(19):e2024144118. doi: 10.1073/pnas.2024144118.


Salmonella is an intracellular pathogen of a substantial global health concern. In order to identify key players involved in Salmonella infection, we performed a global host phosphoproteome analysis subsequent to bacterial infection. Thereby, we identified the kinase SIK2 as a central component of the host defense machinery upon Salmonella infection. SIK2 depletion favors the escape of bacteria from the Salmonella-containing vacuole (SCV) and impairs Xenophagy, resulting in a hyperproliferative phenotype. Mechanistically, SIK2 associates with actin filaments under basal conditions; however, during bacterial infection, SIK2 is recruited to the SCV together with the elements of the actin polymerization machinery (Arp2/3 complex and Formins). Notably, SIK2 depletion results in a severe pathological cellular actin nucleation and polymerization defect upon Salmonella infection. We propose that SIK2 controls the formation of a protective SCV actin shield shortly after invasion and orchestrates the actin cytoskeleton architecture in its entirety to control an acute Salmonella infection after bacterial invasion.

Keywords: Arp2/3 complex; Salmonella; Salmonella-containing vacuole; actin cytoskeleton; host–pathogen interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cells, Cultured
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunoblotting
  • Mice
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Interaction Maps*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteomics / methods
  • RNA Interference
  • Salmonella / physiology
  • Signal Transduction*


  • Actins
  • Phosphoproteins
  • salt-inducible kinase-2, human
  • Protein Serine-Threonine Kinases