**5.** *Salmonella* **pathogenesis**

The favorable outcome of a pathogen is based on its capability to enter a host, evade host defense barrier and initiate infection. *Salmonella* has developed contrasting schedule to destabilize normal host cellular functions that allow it to get involved in and multiple inside the host cell. Depending upon the serotype of *Salmonella* involved and health status of human host, the acuteness of *Salmonella* infection varies. Elderly people, immune-suppression patients and children below 05 years of age are more prone to *Salmonella* infection. The ability of *Salmonella* to invade, replicate and remain alive within the human host makes it more morbific that finally results into harmful mortal disease.

*Salmonella* produces different virulence factors that play an important role in its pathogenicity. These involve (1) the potential to invade the cell (2) a perfect lipopolysaccharide coat (3) to replicate intra-cellularly and (4) feasibly the secretion of toxins [58]. The organisms establish a colony in ileum and colon after ingestion followed by occupying the intestinal epithelium and grows rapidly within the epithelium and lymphoid follicles. *Salmonella* invasion mechanism is partially understood. On epithelial cell surface there is the presence of specific receptors. When the organism incursion occurs, enterocyte membrane goes through disarrangement that results in pinocytosis of organism. Invasion depends on rearrangement of cell cytoskeleton and may be entailed to increase in cellular inositol phosphate and calcium. After invasion, organism has ability to proliferate intra-cellularly thereby escalating to mesenteric lymph nodes and all over the body by systematic circulation; absorbed by reticuloendothelial cells that limits and checks the expansion of an organism. There is a perceptible genetic control involving multiple genes in both chromosomes and plasmids for attachment and invasion. Some organisms has the ability to infect liver, spleen, gall bladder, bone, meninges etc. depending upon the host defense. Human *Salmonella* (gastroenteritis) resides in intestine. However, most serotypes get perished on time. After invading the intestine, most of *Salmonellae* brings on an acute inflammatory response that may lead to ulceration, also they might elaborate cytotoxins that forbid protein synthesis. It is not clear if these cytotoxins play a role in the inflammatory response or ulceration. On the other hand, invasion of the mucosa induces epithelial cells to produce and release pro-inflammatory cytokines such as IL-1, IL-6, IL-8, TNF-2, IFN-U, MCP-1, and GM-CSF. These trigger an acute inflammatory response in the body and may also be accountable to harm the intestine [59]. Due to the inflammatory reaction, symptoms such as fever, chills, stomach pain, leukocytosis, and diarrhea are frequent. Polymorphonuclear leukocytes, blood, and mucus may be seen in the stool.

One of the features of *Salmonella* is non-phagocytic nature on human host cells during invasion [60], where it literally induces its own phagocytosis in order to gain access to its host cell. *Salmonella* pathogenicity islands (SPIs), gene clusters positioned at the major chromosomal DNA region and encoding for the structures required in the invasion activity, provide the remarkable genetics that enable this brilliant technique [61]. Bacteria tend to infiltrate the epithelial cells of the intestinal wall when they enter the digestive tract *via* contaminated water or food. Type III secretion systems, or SPIs, are multi-channel proteins that allow *Salmonella* to infuse its effectors into the cytoplasm *via* the intestinal epithelial cell membrane. The bacterial effectors subsequently activate the signal transduction pathway and lead the host cell's actin cytoskeleton to be rebuilt, causing the epithelial cell membrane to ruffle outward and engulf the bacteria. The membrane ruffle's morphology is similar to the process of phagocytosis [62].

The ability of the *Salmonella* strains to remain in the host cell is important for pathogens as strains lacking this capability are non-virulent [63]. After the host cell engulfs *Salmonella*, the bacterium is enclosed in a membrane compartment called a vacuole, which is formed of the host cell membrane. The presence of the bacterial foreign body activates the host cell immune response under normal circumstances, which result in the fusion of the lysosomes and the secretion of the digestive enzymes to break down the intracellular bacteria. Although, *Salmonella* uses the type III secretion system to inject other effector proteins into the vacuole, it causes the modification of the compartment structure. The re-assembled vacuole obstructs the fusion of the lysosomes and this allows the intracellular survival and replication of the bacteria inside the host cells. The ability of the bacteria to continue within macrophages allows them to be carried in the reticulo-endothelial system (RES) [64].

### Salmonella *Infection and Pathogenesis DOI: http://dx.doi.org/10.5772/intechopen.102061*

The mechanisms of *Salmonella* gastroenteritis and diarrhea are well known now. Only strains that infiltrate the intestinal mucosa are associated with the appearance of an acute inflammatory reaction and diarrhea; the secretion of fluid and electrolytes by the small and large intestines causes the diarrhea. Even though, the secretion is not just an indication of tissue destruction and ulceration, the mechanisms of secretion are indistinct. Unlike *Shigella* and invasive *Escherichia coli*, *Salmonella* infiltrates the intestinal epithelial cells but, do not escape the phagosome. Therefore, the extent of intercellular spread and ulceration of the epithelium is much less. From the basal side of epithelial cells, *Salmonella* escapes into the lamina propria. Systemic spread of the organisms can occur that causes the enteric fever. Following the invasion of the intestinal mucosa, activation of mucosal adenylate cyclase occurs; that results in the increase in cyclic AMP that causes secretion. It is not understood that by which mechanism adenylate cyclase is stimulated; it might involve local production of prostaglandins or other components of the inflammatory reaction.
