**5.1 SPI1**

*Salmonella* species has the capability to penetrate non-phagocytic host cells. For the penetration or invasion to take place, there is requirement of several genes which were first identified for *S. typhimurium* [10]. At the later stages of research, it was established that all the genes responsible for invasion were bunched within a region at centisome 63 of the *Salmonella* chromosome [11]. After that, the second cluster of genes were identified which were required because of the ability of *Salmonella* to proliferate in different organs of the infected host, lead the researchers to designate Invasion Locus *Salmonella* Pathogenicity Island 1 and accordingly newly identified locus as *Salmonella* Pathogenicity Island 2 [12].

The size of SPI-1 is nearly 40 kilo bases in size and encodes a type III secretion system (T3SS) that is needed for BME and intestinal epithelial invasion (**Figure 1**). T3SS are considered as complex macromolecule machines that emerge to bring down the function of host cell by translocation of virulence proteins straight from the bacterial cytoplasm into the host cell. T3SS are also known as injectisomes' or 'molecular needles because of their capability to translocate proteins in a cell contact-dependent manner [13]. T3SS is also found in several species of several Gram-negative bacteria (e.g. *Salmonella*, *Yersinia, Shigella, E. coli, Pseudomonas*) and encompasses at least 20 different subunits that enables these bacteria to translocate specific substrates (or 'effectors') directly into the host cell cytoplasm which exerts a broad range of virulence functions [14]. The mutants of *Salmonella* not having a functional SPI-1 T3SS do not invade epithelial cells in tissue culture [15].

#### **Figure 1.**

*Invasion of* Salmonella *into non-phagocytic cells by SPI1. At the time of contact with host cell, there is injection of different effectors into cytoplasm of host cell by SPI1 encoded T3SS. This leads to stimulation of small rho GTPases that causes massive cytoskeleton rearrangements. This results in intake of bacteria by macropinocytosis. Now, bacteria live in vacuole and the host cells regain a normal architecture. (from Gerlach RG, Hensel M.* Salmonella *pathogenicity islands in host specificity, host pathogen-interactions and antibiotics resistance of* Salmonella enterica*. Berliner und Munchener tierarztliche Wochenschrift. 2007 Jul 1;120(7/8):317).*

There is requirement of at least five translocated proteins adequate invasion of cultured epithelial cells, whereas invasion is more complex and diverse in animal tissues [16]. Two subsets of effector proteins are generated by SPI-1 in which one subset mediates invasion by *Salmonella* of non-phagocytic cells through alteration of active cytoskeleton system of host cell and the other second subset is related with entero-pathogenesis and inflammation of cells of intestinal epithelium. The important effector proteins are summarized in **Table 2**.


#### **Table 2.**

*Important translocated proteins of SP-I of* Salmonella.
