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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. / Alphonse, Noémie; Wanford, Joseph J.; Voak, Andrew A.; Gay, Jack; Venkhaya, Shayla; Burroughs, Owen; Mathew, Sanjana; Lee, Truelian; Evans, Sasha L.; Zhao, Weiting; Frowde, Kyle; Alrehaili, Abrar; Dickenson, Ruth E.; Munk, Mads; Panina, Svetlana; Mahmood, Ishraque F.; Llorian, Miriam; Stanifer, Megan L.; Boulant, Steeve; Berchtold, Martin W.; Bergeron, Julien R. C.; Wack, Andreas; Lesser, Cammie F.; Odendall, Charlotte.

I: Cell, Bind 185, Nr. 13, 2022, s. 2354-2369.e17.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Alphonse, N, Wanford, JJ, Voak, AA, Gay, J, Venkhaya, S, Burroughs, O, Mathew, S, Lee, T, Evans, SL, Zhao, W, Frowde, K, Alrehaili, A, Dickenson, RE, Munk, M, Panina, S, Mahmood, IF, Llorian, M, Stanifer, ML, Boulant, S, Berchtold, MW, Bergeron, JRC, Wack, A, Lesser, CF & Odendall, C 2022, 'A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling', Cell, bind 185, nr. 13, s. 2354-2369.e17. https://doi.org/10.1016/j.cell.2022.04.028

APA

Alphonse, N., Wanford, J. J., Voak, A. A., Gay, J., Venkhaya, S., Burroughs, O., Mathew, S., Lee, T., Evans, S. L., Zhao, W., Frowde, K., Alrehaili, A., Dickenson, R. E., Munk, M., Panina, S., Mahmood, I. F., Llorian, M., Stanifer, M. L., Boulant, S., ... Odendall, C. (2022). A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell, 185(13), 2354-2369.e17. https://doi.org/10.1016/j.cell.2022.04.028

Vancouver

Alphonse N, Wanford JJ, Voak AA, Gay J, Venkhaya S, Burroughs O o.a. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell. 2022;185(13):2354-2369.e17. https://doi.org/10.1016/j.cell.2022.04.028

Author

Alphonse, Noémie ; Wanford, Joseph J. ; Voak, Andrew A. ; Gay, Jack ; Venkhaya, Shayla ; Burroughs, Owen ; Mathew, Sanjana ; Lee, Truelian ; Evans, Sasha L. ; Zhao, Weiting ; Frowde, Kyle ; Alrehaili, Abrar ; Dickenson, Ruth E. ; Munk, Mads ; Panina, Svetlana ; Mahmood, Ishraque F. ; Llorian, Miriam ; Stanifer, Megan L. ; Boulant, Steeve ; Berchtold, Martin W. ; Bergeron, Julien R. C. ; Wack, Andreas ; Lesser, Cammie F. ; Odendall, Charlotte. / A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. I: Cell. 2022 ; Bind 185, Nr. 13. s. 2354-2369.e17.

Bibtex

@article{43661ba61ee74c438f82f039921cdd38,

title = "A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling",

abstract = "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.",

keywords = "Animals, Antiviral Agents, Calcium Signaling, Epithelial Cells/metabolism, Interferons/metabolism, Mice, Virulence Factors/metabolism",

author = "No{\'e}mie Alphonse and Wanford, {Joseph J.} and Voak, {Andrew A.} and Jack Gay and Shayla Venkhaya and Owen Burroughs and Sanjana Mathew and Truelian Lee and Evans, {Sasha L.} and Weiting Zhao and Kyle Frowde and Abrar Alrehaili and Dickenson, {Ruth E.} and Mads Munk and Svetlana Panina and Mahmood, {Ishraque F.} and Miriam Llorian and Stanifer, {Megan L.} and Steeve Boulant and Berchtold, {Martin W.} and Bergeron, {Julien R. C.} and Andreas Wack and Lesser, {Cammie F.} and Charlotte Odendall",

year = "2022",

doi = "10.1016/j.cell.2022.04.028",

language = "English",

volume = "185",

pages = "2354--2369.e17",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "13",

}

RIS

TY - JOUR

T1 - A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling

AU - Alphonse, Noémie

AU - Wanford, Joseph J.

AU - Voak, Andrew A.

AU - Gay, Jack

AU - Venkhaya, Shayla

AU - Burroughs, Owen

AU - Mathew, Sanjana

AU - Lee, Truelian

AU - Evans, Sasha L.

AU - Zhao, Weiting

AU - Frowde, Kyle

AU - Alrehaili, Abrar

AU - Dickenson, Ruth E.

AU - Munk, Mads

AU - Panina, Svetlana

AU - Mahmood, Ishraque F.

AU - Llorian, Miriam

AU - Stanifer, Megan L.

AU - Boulant, Steeve

AU - Berchtold, Martin W.

AU - Bergeron, Julien R. C.

AU - Wack, Andreas

AU - Lesser, Cammie F.

AU - Odendall, Charlotte

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Animals

KW - Antiviral Agents

KW - Calcium Signaling

KW - Epithelial Cells/metabolism

KW - Interferons/metabolism

KW - Mice

KW - Virulence Factors/metabolism

U2 - 10.1016/j.cell.2022.04.028

DO - 10.1016/j.cell.2022.04.028

M3 - Journal article

C2 - 35568036

VL - 185

SP - 2354-2369.e17

JO - Cell

JF - Cell

SN - 0092-8674

IS - 13

ER -

ID: 312499011

Biologisk Institut