How Salmonella infections promote cancer development

This project, in collaboration with the Dutch National Institute for Public Health and the Environment (RIVM), explored the molecular mechanism(s) that allow Salmonella infection to promote colon tumor formation. 

Salmonellae are associated epidemiologically and experimentally with colon cancer. To understand how Salmonella induces cell transformation, we performed multi-omics and phenotypic analyses of Salmonella clinical strains isolated from patients later diagnosed with colon cancer (case strains), and control strains from patients without cancer. We show that high transformation efficiency is a frequent intrinsic feature of clinical (case and control) salmonellae, yet case strains showed higher transformation efficiency than control strains. Transformation efficiency correlates with gene expression, nutrient utilization, and intracellular virulence, but not with genetic features, suggesting a phenotypic convergence of Salmonella strains resulting in cell transformation. We show that both bacterial entry and intracellular replication are required for host cell transformation and are associated with hyper-activation of the mTOR pathway. Strikingly, transiently inactivating mTOR through chemical inhibition reverses the transformation phenotype instigated by Salmonella infection. This suggests that targeting the mTOR pathway could prevent the development of Salmonella-induced tumors.

Associated publications:

Stévenin V, Neefjes J*. 2025 (comment)

Salmonella, the insidious contributor to gallbladder and colon cancers

Nature Cancer Review. doi:10.1038/s41568-025-00812-z

Stévenin V#*, Coipan C#, Duijster J, van Elsland D, Voogd L,  Bigey L, van Hoek A, Wijnands L, Jansen L, Akkermans J, Neefjes-Borst A, Franz E, Mughini-Gras L, Neefjes J*. 2024

Multi-omics analyses of cancer-linked clinical salmonellae reveal bacterial-induced host metabolic shift and mTOR-dependent cell transformation

Cell Reports. 43(11):114931. doi:10.1016/j.celrep.2024.114931 (.pdf)

Stévenin V*, Neefjes J. 2023

Soft agar colony formation assay to quantify mouse embryonic fibroblast transformation after Salmonella infection

STAR Protocols. 4(3):102379. doi: 10.1016/j.xpro.2023.102379 (.pdf)

van Elsland D#, Duijster J#, Zhang J#, Stévenin V, Zhang Y, Zha L, Xia Y, Franz E, Sun J*, Mughini-Gras L*, Neefjes J*. 2022

Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth. 

Cell Reports Medicine. 3: 100852. doi: 10.1016/j.xcrm.2022.100852 (.pdf)

Associated outreach activity:

Deduction game: Help the scientists find what makes some bacteria more likely to give cancer.