**7. Pathogenicity**

Pathogenicity of *Salmonella* is dependent on the serovar and the host. However, factors that influencing serovar–host specificity are not well known [56]. The basic of *Salmonella* virulence mechanism is associated with the invasion of intestinal mucosa and multiplication in gut-associated lymphoid tissue (GALT). *Salmonella* will invade non-phagocytic cells in the intestine by promoting their self-uptake in a complicated and dynamic process similar to phagocytosis [57].

*Salmonella* infection in human can cause either systemic disease with rare association with food poisoning or one that can cause enteritis or localised disease. In oral infection, *Salmonella* must go through a variety of host defence mechanisms and different environments in the stomach during the progression of infection before successfully entering the intestinal tract. *Salmonella* adapted to these settings by using a broad variety of genes that may be reflected as virulence determinants, including *Salmonella*-specific virulence genes, housekeeping genes and regulatory genes. Virulence genes involved in invasion and critical for intracellular survival are grouped in large chromosomal DNA regions termed as *Salmonella* pathogenicity islands (SPIs). SPIs often exist in huge clusters of genes that are found in the vast chromosomal DNA regions that contribute to a certain virulence phenotype that manifests at a given period during infection [58].

Significant pathogenicity islands in *Salmonella* are SPI-1 and SPI-2. SPI-1 being the most well-defined SPI and required for virulence encodes the type III protein secretion system (T3SS), which injects effector proteins into host cells and provides the essential

mechanism for intestinal invasion and enteritis formation [59]. The T3SS is the most significant *Salmonella* virulence factor. SPI-1 genes are involved in host cell invasion, immune cell recruitment, apoptosis, and biofilm formation, while other transcription factors encoded outside SPI-1 engage in the expression of SPI-1-encoded genes. SPI-1's regulatory network is intricate and extremely important [37]. SPI-1's ubiquity is conserved and essential for *Salmonella* pathogenicity, as shown by its direct role in invasion. The T3SS of SPI-1 and SPI-2 has been suggested to be inversely regulated [52, 53].

This is an appealing hypothesis as *Salmonella* systemic infection to a host must first infiltrate M cells, where SPI-1 expression is required, and then replicate within macrophages, where SPI-2 expression is required. Mutations in SPI-2 genes encoding the type III secretion apparatus, on the other hand, diminish the expression of genes encoding a transcriptional activator of SPI-1 (*sipC*, *prgK* and *hilA*), suggesting the interaction between SPI-1 and SPI-2 [60]. Over the previous decade, around 30 SPI-2 T3SS effectors have been discovered. Thirteen of them are involved in the regulation of *Salmonella*-containing vacuole (SCV) membrane dynamics, the location of *Salmonella*-containing vacuole (SCV) inside host cells, immunological modulation, cytoskeletal changes and the motility of infected cells, among other things [61].
