Epithelial cells are cells that come from surfaces of your body, such as the skin, blood vessels, urinary tract, or organs. They serve as a barrier between the inside and outside of your body, and protect it from viruses. A new finding by the National Institute of Allergy and Infectious Diseases (NIAID) scientists at Rocky Mountain Laboratories demonstrates how Salmonella bacteria use intestinal epithelial cells to colonize the gut. The findings may lead to developing new treatments that help reduce the pathogen.
Their work was published in the journal Cell Host & Microbe in a paper titled, “Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium.”
“Persistent and intermittent fecal shedding, hallmarks of Salmonella infections, are important for fecal-oral transmission,” wrote the researchers. “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.”
The CDC estimates Salmonella bacteria cause about 1.35 million infections, 26,500 hospitalizations, and 420 deaths in the United States every year. Antibiotics typically are used only to treat people who have severe illness or who are at risk for it.
Intestinal epithelial cells provide a barrier of protection for the GI tract. These cells prevent pathogens from spreading to deeper tissues. However, in previous studies, NIAID scientists had observed that some Salmonella replicate rapidly in the cytosol—the fluid portion—of intestinal epithelial cells. This finding prompted the scientists to question whether ejecting the infected cell amplifies rather than eliminates the bacteria.
“Here, we engineered STm that self-destruct in the cytosol (STmCytoKill), but replicates normally in the SCV, to examine the role of cytosolic STm in infection,” wrote the researchers.
The team infected mice with the self-destructing Salmonella bacteria and observed that replication in the cytosol of mouse intestinal epithelial cells is critical for colonization of the GI tract and fuels fecal shedding. The scientists hypothesize that, by hijacking the epithelial cell response, Salmonella amplify their ability to invade neighboring cells and seed the intestine for fecal shedding.
“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,” concluded the researchers.