MAP4Ks drive cell death in response to Salmonella SpvB-induced actin depolymerisation
Author(s)
Type
Journal Article
Abstract
Many pathogens target the host actin cytoskeleton through the delivery of actin depolymerizing toxins, including mono-ADP-ribosyltransferases (mART), ultimately triggering host cell death. Despite the importance of mARTs in pathogen virulence, it remains unclear whether actin ribosylation is required for mART-dependent cell death, and how actin depolymerization leads to cell death. Using the non-typhoidal Salmonella enterica Typhimurium-encoded mART, SpvB, we report that cell death is induced exclusively through ribosylation of actin. We found cell death to be morphologically and mechanistically distinct from apoptosis as well as any previously reported mode of cell death. Instead, our data identify the Hippo signaling MAP4Ks as the essential host cell sensors of actin depolymerization signaling through JNK to facilitate vacuolization and host cell death. Cell death following treatment of cells with the actin depolymerizing agent latrunculin A followed the same pathway, identifying a conserved mechanism of cell death. Therefore, we identify MAP4K family members as key regulators of an atypical caspase-independent cell death induced by actin depolymerization, building on our understanding of host-cell death signaling and mechanisms of bacterial virulence.
Date Issued
2026-05-20
Date Acceptance
2026-04-28
Citation
mBio, 2026, 17 (6)
ISSN
2161-2129
Publisher
American Society for Microbiology
Journal / Book Title
mBio
Volume
17
Issue
6
Copyright Statement
© 2026 Pallett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Publication Status
Published
Article Number
e00655-26
Date Publish Online
2026-05-20