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

IF 3.1 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Microbiology Pub Date : 2026-04-13 DOI:10.1111/mmi.70067

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

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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.

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肠沙门氏菌伤寒毒素诱导ISG15应答，介导宿主细胞存活并对抗细胞内感染

伤寒毒素是细菌病原体肠沙门氏菌伤寒血清型的分泌毒力因子，与伤寒和慢性感染有关。该毒素在人体细胞中引起DNA损伤反应，其特征是细胞周期阻滞和细胞膨胀，导致细胞衰老和细菌负担增加。为了更好地了解宿主对伤寒毒素的反应，我们对中毒的宿主细胞进行了转录组学分析，发现毒素诱导了与I型干扰素反应相关的基因的表达，包括泛素样蛋白ISG15。ISG15以STING依赖的方式上调，减少细菌负担，并被发现对宿主细胞在伤寒毒素和干扰素反应中存活至关重要。这突出表明ISG15是宿主细胞防御伤寒毒素的重要组成部分。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Microbiology 生物-生化与分子生物学

CiteScore

7.20

自引率

5.60%

发文量

132

审稿时长

1.7 months

期刊介绍： Molecular Microbiology, the leading primary journal in the microbial sciences, publishes molecular studies of Bacteria, Archaea, eukaryotic microorganisms, and their viruses. Research papers should lead to a deeper understanding of the molecular principles underlying basic physiological processes or mechanisms. Appropriate topics include gene expression and regulation, pathogenicity and virulence, physiology and metabolism, synthesis of macromolecules (proteins, nucleic acids, lipids, polysaccharides, etc), cell biology and subcellular organization, membrane biogenesis and function, traffic and transport, cell-cell communication and signalling pathways, evolution and gene transfer. Articles focused on host responses (cellular or immunological) to pathogens or on microbial ecology should be directed to our sister journals Cellular Microbiology and Environmental Microbiology, respectively.