*2.1.2.2 ShdA*

S*hdA* gene is located in the 25-kb pathogenicity island called CS54 which is present only in *S*. *enterica* subspecies *enterica* [51]. ShdA is a large fibronectin/collagen I-binding outer membrane protein which is induced *in vivo* in the murine caecum [52]. It is required for Typhimurium colonization in the murine caecum and Peyer's patches of the terminal ileum [53] and for efficient and prolonged shedding of the organism in feces [51].

### *2.1.2.3 BapA*

BapA is a huge surface-associated protein and secreted via its downstream type I secretion system, BapBCD. BapA contributes to murine intestinal colonization and

**173**

*enteropathogenesis*

(**Figure 1**).

*Virulence Determinants of Non-typhoidal* Salmonellae *DOI: http://dx.doi.org/10.5772/intechopen.88904*

with the wild-type strain [54].

*2.1.2.4 SiiE*

cells [55].

subsequent organ invasion. Mice orally inoculated with *BapA*-deficient strain survived longer and have a significant reduction in mortality rate than those inoculated

*SiiE* is a SPI4-encoded protein and works as the substrate protein of the T1SS. SiiE is secreted into the culture medium but mediates contact-dependent adhesion to epithelial cell surfaces. SiiE codes for a giant non-fimbrial adhesion of 600 kDa and consists of 53 repeats of immunoglobulin domains; this is a T1SSsecreted protein that functions as a non-fimbrial adhesion in binding to eukaryotic

Shortly after adhesion to a host cell, *Salmonella* invasion proceeds as a consequence of the activation of host cell signaling pathways leading to profound cytoskeletal rearrangements [56]. These internal modifications dislocate the normal epithelial brush border and induce the subsequent formation of membrane ruffles that engulf adherent bacteria in barge vesicles called *Salmonella* containing vacuoles (SCVs), which is the only intracellular compartment where *Salmonella* cells survive and replicate [57, 58]. Simultaneously, induction of secretory response in the intestinal epithelium initiates recruitment and transmigration of phagocytes from the submucosal space into the intestinal lumen. Alternatively, *Salmonella* cells may be directly engulfed by dendritic cells from the submucosa. Taken up During SCV maturation, *Salmonella* induces *de novo* formation of an F-actin meshwork around bacterial vacuoles, a process which is termed vacuole-associated action polymerization (VAP) and is important for maintenance of the integrity of the vacuole membrane [59]. Furthermore, intracellular *Salmonella* can induce the formation of long filamentous membrane structure called *Salmonella*-induced filaments (SIFs) [60], which may lead to an increased availability of nutrients within the SCV [61]. A fraction of SCVs transcytose to the basolateral membrane. Once across the intestinal epithelium, *Salmonella* are engulfed by phagocytes and internalized again with SCVs, triggering a response similar to that reported inside epithelial and M cells to ensure bacterial survival and replication [62]. The pathogenic bacterium must at this stage employ many virulence strategies to evade the host defense mechanisms

The majority of the virulence determinants are located within highly conserved SPIs on the chromosome, while others are either on a virulence plasmid (pSLT) or elsewhere in the chromosome. To date, 21 SPIs have been identified in *Salmonella*, and the generalist *S. typhimurium* and the invasive *S. typhi* genomes share 11 (SPIs-1 to 6, 9, 11, 12, 13 and 16). Two SPIs namely SPI-8 and 10 were initially found in *S. typhi* and without counterparts in *S. typhimurium* chromosome; SPI-14 is specific to *S*. *typhimurium*, while *SPIs*-7, 15, 17 and 18 are specific to *S. typhi*; and SPIs-19, 20 and 21 are absent in both of them [63]. Because of the prominence of the SPIs in pathogenesis, the virulence factors encoded on the major SPIs, SPI-1 to SPI-5 are described below, and their respective functions summarized (**Tables 2** and **3**).

*2.2.1 SPI-1 mediates contact-dependent invasion of the intestinal epithelium and* 

SPI-1 codes for several effector proteins that trigger invasion of epithelial cells by mediating actin cytoskeletal rearrangements and hence internalization of the

**2.2 Intestinal phase: invasion and intracellular survival**

subsequent organ invasion. Mice orally inoculated with *BapA*-deficient strain survived longer and have a significant reduction in mortality rate than those inoculated with the wild-type strain [54].
