Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection

Daniel S. Stark; Michelle King; Angela E. M. Ibler; Salma Srour; Francesca Brown; James Sheffield; Nadia Baseer; Ellen G. Vernon; Yifeng Zhang; Christopher Staples; Lilliana Radoshevich; Daniel Humphreys

doi:10.1111/mmi.70067

Back

Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection

Journal article

Open access

Peer reviewed

Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection

Daniel S. Stark, Michelle King, Angela E. M. Ibler, Salma Srour, Francesca Brown, James Sheffield, Nadia Baseer, Ellen G. Vernon, Yifeng Zhang, Christopher Staples, …

Molecular microbiology

04/13/2026

DOI: 10.1111/mmi.70067

PMID: 41973907

Files and links (1)

url

https://doi.org/10.1111/mmi.70067View

Published (Version of record) Open Access

Abstract

The typhoid toxin is a secreted virulence factor of typhoidal serovars of the bacterial pathogen Salmonella enterica implicated in typhoid fever and chronic infections. The toxin causes a DNA damage response in human cells, characterised by cell‐cycle arrest and cellular distension, resulting in cellular senescence and increased bacterial burden. To better understand host responses to typhoid toxin, we performed a transcriptomic analysis of intoxicated host cells and found that the toxin induced expression of genes relating to the type‐I interferon response, including the ubiquitin‐like protein ISG15. ISG15 was upregulated in a STING‐dependent manner, reduced bacterial burden, and was found to be critical to host cell survival in response to the typhoid toxin and interferon. This highlights ISG15 as an important component of the host cell defence to the typhoid toxin.

Details

Title: Subtitle: Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection
Creators: Daniel S. Stark - University of Sheffield
Michelle King - University of Sheffield
Angela E. M. Ibler - University of Sheffield
Salma Srour - University of Sheffield
Francesca Brown - University of Sheffield
James Sheffield - University of Sheffield
Nadia Baseer - University of Sheffield
Ellen G. Vernon - Bangor University
Yifeng Zhang - University of Iowa
Christopher Staples - Bangor University
Lilliana Radoshevich - University of Iowa
Daniel Humphreys - University of Sheffield
Resource Type: Journal article
Publication Details: Molecular microbiology
DOI: 10.1111/mmi.70067
PMID: 41973907
NLM abbreviation: Mol Microbiol
ISSN: 0950-382X
eISSN: 1365-2958
Publisher: Wiley
Grant note: Medical Research Council: MR/N013840/1, MR/K015753 UK Research and Innovation: MR/S034390/1, MR/X02329X/1, MR/X024040/1 National Institute of General Medical Sciences: R35GM137961
This work was supported by UK Research and Innovation (MR/S034390/1, MR/X02329X/1 and MR/X024040/1); Medical Research Council (MR/N013840/1 and MR/K015753); National Institute of General Medical Sciences (R35GM137961).
Language: English
Electronic publication date: 04/13/2026
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9985153393702771

Metrics

1 Record Views