**2. Pathophysiology of** *Salmonella*

*Salmonella* is noted to cause diverse disease spectrum in humans and animals, varying from localized inflammation and gastroenteritis to typhoid fever which can lead to life-threatening systemic infection. The prime issue is that of asymptomatic healthy carriers who possibly shed bacteria in feces causing risk to community. There is diversity seen among certain *Salmonella* serovars based on host adaptation, such as *Salmonella* Typhi, *Salmonella* Paratyphi, and *Salmonella* Sendai are known to be very well adapted to only human host while *Salmonella* Typhimurium and *Salmonella* Enteritidis has a broad host range infecting animals and humans. Others produce diseases in farm animals like S. Choleraesuis in swine, S. Gallinarum in fowl. *Salmonella* Dublin (cattle) and Arizonae (reptiles) are mainly adapted to an animal species and seldom infect humans [1].

## **3. Pathogenesis of** *Salmonella*

For the *Salmonella* infection to commence the bacteria is ingested through contaminated food and water. The infectious dose varies considerably ranging between 103 –106 colony-forming units [2].

The first hurdle to *Salmonella* colonization is acidity of stomach and certain situations which either decreases stomach acidity (antacids, proton pump inhibitors, achlorhydric disease) or integrity of intestine (previous surgery of gastrointestinal tract, altered intestinal flora due to antibiotic use, inflammatory bowel disease) increases the chances of *Salmonella* infection [3].

Salmonellae exhibit an adaptive acid tolerance response on exposure to acid in vitro that possibly eases its survival in the stomach and movement to the small intestine.

When it reaches the small intestine, it attaches to the mucosal epithelial cells by fimbriae. Now, the penetration of the mucosal epithelium is achieved by *bacteriamediated endocytosis* (BME) [4].

When the bacteria adheres to the apical epithelial surface, an extensive cytoskeletal rearrangements is followed shortly which disturbs the normal epithelial brush border prompting the configuration of membrane ruffles. These membrane ruffles reach out and encloses adherent bacteria in large vesicles. M cells (specialized cells overlying the Peyer's patches) are probably considered the primary portal of entry in case of Enteric fever and the generalized intrusion of enterocytes is thought to play a prominent role in enteritis caused by Non-Typhoidal *Salmonella* (NTS) serotypes [5].

There are several large insertions in the genome of *Salmonella* that are considered to arise from bacteriophages or plasmids, called as the *Salmonella* pathogenicity islands (SPIs). These SPIs encode genes that are crucial for survival in the host. The virulence genes are responsible for invasion, survival, and extra intestinal spread. For instance, Salmonellae encode a type III secretion system (T3SS) within *Salmonella* pathogenicity island 1 (the SPI-1 T3SS), which is necessary for bacteriamediated endocytosis and epithelial invasion in the intestine.

#### **4. Definitions**

#### **4.1 Genomic Island**

Genomic islands (GIs) such as integrative and conjugative elements (ICEs) and integrative mobilizable elements (IMEs) are clusters of genes inside a bacterial genome which seems to be acquired by horizontal gene transfer [6]. Initially noticed in pathogenic bacteria, designated as pathogenicity islands because they carried virulence genes or other pathogenicity factors, now are also identified in various non-pathogenic bacteria. Therefore, GIs are frequently named based on the adaptive properties they bestow such as metabolic islands, antibiotic resistance islands, symbiosis islands, pathogenicity islands etc. [7]. Furthermore, GIs bless their hosts with new traits, like resistance to antimicrobials and enhanced virulence.

#### **4.2 Pathogenicity island (PAI)**

Pathogenicity islands are a definite class of GIs acquired by microorganisms by horizontal gene transfer. They constitute large genomic regions (10–200 kilobases in size) that are integrated in the genome of pathogenic bacteria and are not seen in non-pathogenic bacteria of the same or closely related species [6]. The concept of


#### **Table 1.** *Features of Pathogenicity Islands.*

pathogenicity islands was established in the late 1980s by Jorg Hacker and his colleagues while probing the genetic grounds of virulence of uropathogenic *Escherichia coli* strains 536 and J96 [8]. The important features of PIs are summarized in **Table 1** [8].
