SIK2 orchestrates actin-dependent host response upon Salmonella infection

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Marcel Hahn
  • Adriana Covarrubias-Pinto
  • Lina Herhaus
  • Shankha Satpathy
  • Kevin Klann
  • Keith B Boyle
  • Christian Münch
  • Krishnaraj Rajalingam
  • Felix Randow
  • Choudhary, Chuna Ram
  • Ivan Dikic

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.

Original languageEnglish
Article numbere2024144118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number19
Number of pages10
ISSN0027-8424
DOIs
Publication statusPublished - 2021

ID: 261514207