A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling

Noémie Alphonse, Joseph J. Wanford, Andrew A. Voak, Jack Gay, Shayla Venkhaya, Owen Burroughs, Sanjana Mathew, Truelian Lee, Sasha L. Evans, Weiting Zhao, Kyle Frowde, Abrar Alrehaili, Ruth E. Dickenson, Mads Munk, Svetlana Panina, Ishraque F. Mahmood, Miriam Llorian, Megan L. Stanifer, Steeve Boulant, Martin W. BerchtoldJulien R.C. Bergeron, Andreas Wack, Cammie F. Lesser, Charlotte Odendall*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Interferons (IFNs) induce an antimicrobial state, protecting tissues from infection. Many viruses inhibit IFN signaling, but whether bacterial pathogens evade IFN responses remains unclear. Here, we demonstrate that the Shigella OspC family of type-III-secreted effectors blocks IFN signaling independently of its cell death inhibitory activity. Rather, IFN inhibition was mediated by the binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II and downstream JAK/STAT signaling. The growth of Shigella lacking OspC1 and OspC3 was attenuated in epithelial cells and in a murine model of infection. This phenotype was rescued in both models by the depletion of IFN receptors. OspC homologs conserved in additional pathogens not only bound CaM but also inhibited IFN, suggesting a widespread virulence strategy. These findings reveal a conserved but previously undescribed molecular mechanism of IFN inhibition and demonstrate the critical role of Ca2+ and IFN targeting in bacterial pathogenesis.

Original languageEnglish
Pages (from-to)2354-2369.e17
Issue number13
Publication statusPublished - 23 Jun 2022


  • Ca
  • calcium
  • calmodulin
  • CaMKII
  • host-pathogen interactions
  • interferons
  • ISG
  • OspC1
  • OspC3
  • Shigella
  • T3SS


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