Salmonella is a widespread bacterium that causes salmonellosis in both humans and animals. This foodborne pathogen, belonging to the Enterobacteriaceae family, is a global public health concern. Salmonella encompasses over 2,600 identified serovars, with transmission often occurring through contaminated food and water, particularly animal-derived products like poultry and eggs. The severity of illness can range from mild gastroenteritis to more severe systemic diseases, depending on the specific Salmonella serotype and the host’s immune status.
Initial Colonization of the Intestine
Upon ingestion, Salmonella bacteria navigate the acidic environment of the stomach and reach the small and large intestines. This initial colonization is an important step in establishing an infection. The bacteria interact with the intestinal lining, which forms a single layer of specialized epithelial cells.
Salmonella can attach to these epithelial cells and invade. They induce their uptake by these cells, sometimes by causing membrane ruffles. While some Salmonella replicate rapidly within the cytosol of intestinal epithelial cells, these infected cells are often ejected into the gut lumen, spreading through fecal shedding. This environment allows for initial growth and replication.
Replication within Gut-Associated Tissues
After breaching the intestinal lining, Salmonella invades specialized gut-associated lymphoid tissues. These tissues include Peyer’s patches and the draining mesenteric lymph nodes. Salmonella can preferentially enter M cells and then be transported to underlying immune cells.
Once inside these tissues, Salmonella is taken up by and replicates within immune cells, particularly macrophages. Macrophages are a type of white blood cell that engulf and destroy pathogens, but Salmonella has evolved strategies to survive and multiply within them. These gut-associated lymphoid tissues serve as important sites for bacterial proliferation, acting as a bridge for dissemination from the gut to other parts of the body.
Systemic Dissemination in Typhoidal Infections
Typhoidal Salmonella serovars, such as Salmonella Typhi and Salmonella Paratyphi, can progress to a systemic disease. After replication in these tissues, these pathogens can disseminate throughout the body via the bloodstream and lymphatic system. This widespread distribution leads to enteric fever, also known as typhoid fever.
Typhoidal Salmonella replicates in internal organs. Common sites include the liver, spleen, and bone marrow, where the bacteria multiply within macrophages. The gallbladder is an important site of replication and can become a chronic reservoir for Salmonella Typhi. Salmonella can reach the gallbladder through the bloodstream or bile ducts, and its ability to form biofilms on gallstones contributes to long-term persistence and asymptomatic carriage, aiding disease spread.
Strategies for Intracellular Replication
Salmonella’s ability to grow and replicate within host cells, especially macrophages, is an important strategy for its persistence and dissemination. Upon invading a host cell, Salmonella resides within a membrane-bound compartment called the Salmonella-containing vacuole (SCV). This vacuole is a modified phagosome that normally fuses with lysosomes to destroy engulfed pathogens.
Salmonella modifies the SCV environment to avoid destruction and create a niche for replication. This involves the injection of bacterial effector proteins into the host cell cytoplasm, which manipulate host cell processes. For instance, the bacteria can hijack the host’s endosomal system to stabilize the SCV and promote the formation of Salmonella-induced filaments (SIFs), which are tubular structures radiating from the SCV. These intracellular strategies allow Salmonella to survive, replicate, and use immune cells like macrophages as a “Trojan horse” to travel within the host.