1. Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium.
- Author
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Chong A, Cooper KG, Kari L, Nilsson OR, Hillman C, Fleming BA, Wang Q, Nair V, and Steele-Mortimer O
- Subjects
- Animals, Female, HeLa Cells, Humans, Intestines microbiology, Male, Mice, Mice, Inbred C57BL, Salmonella typhimurium genetics, Salmonella typhimurium growth & development, Vacuoles microbiology, Cytosol microbiology, Epithelial Cells microbiology, Feces microbiology, Salmonella Infections microbiology, Salmonella typhimurium physiology
- Abstract
Persistent and intermittent fecal shedding, hallmarks of Salmonella infections, are important for fecal-oral transmission. In the intestine, Salmonella enterica serovar Typhimurium (STm) actively invades intestinal epithelial cells (IECs) and survives in the Salmonella-containing vacuole (SCV) and the cell cytosol. Cytosolic STm replicate rapidly, express invasion factors, and induce extrusion of infected epithelial cells into the intestinal lumen. Here, we engineered STm that self-destruct in the cytosol (STm
CytoKill ), but replicates normally in the SCV, to examine the role of cytosolic STm in infection. Intestinal expansion and fecal shedding of STmCytoKill are impaired in mouse models of infection. We propose a model whereby repeated rounds of invasion, cytosolic replication, and release of invasive STm from extruded IECs fuels the high luminal density required for fecal shedding., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)- Published
- 2021
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