Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection
Year: 2026
Type: article
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.
Source: Molecular Microbiology
DOI: 10.1111/mmi.70067
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,430
Awards: G1012736252, G1308665568, G1919933049, Acute senescence: a novel host defence counteracting typhoidal Salmonella, G2970072724, The typhoid toxin of Salmonella Typhi - a new disease mechanism and a strategy for combatting drug-resistant typhoid and chronic carriage in humans, Regulation of chemosensitivity by the novel daughter strand gap suppressor MRNIP, DTP Bid Led by University of Sheffield, Discovery of Novel Mechanisms of Action of Ubiquitin-Like Proteins in Cellular Stress Pathways, G6397405195
OpenAlex ID: W7154053333