Virginie Stévenin
Leiden University Medical Center, The Netherlands
Cross-kingdom intracellular interactions: Mechanistic insights and long-term consequences
To survive and replicate within a cell, intracellular bacteria, viruses, or parasites, must accommodate the intracellular environment to fulfill their needs. In response to this invasion, the host cell initiates defense mechanisms to eliminate the pathogen. My research tackles these highly dynamic intracellular cross-kingdom interactions and their long-term consequences on the host, such as cancer promotion.
Mostly focusing on unpublished data, the first part of my talk will present our recent findings of a new molecular mechanism used by the intracellular bacteria Salmonella to manipulate the host cell endocytic system. Here, we used high-resolution time-lapse microscopy of endogenously tagged cell lines infected by Salmonella to decipher post-translational modification-dependent shift of the dynamics of small GTPases during infection. While this dynamic manipulation of the endocytic system appeared critical for the intracellular proliferation of the infection, it is also a newly identified mechanism of endocytic trafficking.
The second part of the talk will address a long-term consequence of some intracellular bacterial infections: the promotion of tumor development. My postdoc team showed in 2015 that Salmonella infection can promote host cell transformation, leading to gallbladder carcinoma in the case of Typhoidal Salmonella and colon cancer for Non-Typhoidal Salmonella, but the mechanism was poorly understood. By collaborating with the Dutch National Institute for Public Health and Environment (RIVM), we collected Salmonella clinical strains isolated from patients diagnosed with colon cancer >1 year after Salmonella infection, and control strains isolated from patients who did not develop colon cancer. Multi-omic and phenotypic analyses of cancer-associated clinical Salmonella reveal that bacterial intracellular replication induces metabolism-dependent cell transformation, opening a new path for mechanistic studies of infection-induced tumorigenesis.
Selected publications
- Stévenin V, Coipan C, Duijster J, van Elsland D, Voogd L, van Hoek A, Wijnands L, Jansen L, Akkermans J, Neefjes-Borst A, Franz E, Mughini-Gras L, Neefjes J. (2023). Colon cancer and cell transformation by clinical Salmonella strains are associated with bacterial virulence and intracellular fitness. bioRxiv. 2023.10.19.562874. doi: 10.1101/2023.10.19.562874
- 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
- Berlin I, Sapmaz A, Stévenin V, Neefjes J. (2023). Ubiquitin and its relatives as wizards of the endolysosomal system. Journal of Cell Science. 136 (4): jcs260101. doi: 10.1242/jcs.260101
- 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
- Stévenin V, Neefjes J. (2022). Control of host PTMs by intracellular bacteria: an opportunity towards novel anti-infective agents. Cell Chemical Biology. 29(5):741-756. doi: 10.1016/j.chembiol.2022.04.004
- Stévenin V, Giai Gianetto Q, Duchateau M, Matondo M, Enninga J, Chang YY. (2021). Purification of infection-associated macropinosomes by magnetic isolation for proteomic characterization. Nature Protocols. 16(11):5220-5249. doi: 10.1038/s41596-021-00610-5
- Stévenin V, Chang YY, Le Toquin Y, Duchateau M, Gianetto QG, Luk CH, Salles A, Sohst V, Matondo M, Reiling N, Enninga J. (2019). Dynamic growth and shrinkage of the Salmonella-containing vacuole determines the intracellular pathogen niche. Cell Reports. 29(12):3958-3973.e7. doi: 10.1016/j.celrep.2019.11.049