**4. Clinical manifestations**

NTS infections can cause several clinical symptoms depending on the type of serovar and host factors in humans. NTS symptoms are generally non-specific and hence their identification is a challenging task particularly in areas where laboratory diagnosis facilities are not accessible. Most commonly, *Salmonella* causes self limiting gastroenteritis in human beings. After an incubation period of 6–72 h (mean 24 h), there is sudden onset of nausea, vomiting, abdominal pain and tenderness, followed by mild to severe watery diarrhea and sometimes diarrhea may contain blood and mucus. The stool examination reveals a moderate number of polymorphonuclear leukocytes and blood. Fever is seen in about 70% of patients. Usually, symptoms subside within 2–7 days in healthy children. In certain high-risk groups, like in neonates, young infants, and immunodeficient individuals symptoms may persist for several weeks. As a complication of gastroenteritis, transient bacteremia may occur in some patients (reported incidences in approximately 5% of the patients) [32]. Certain serotypes i.e. *S*. Choleraesuis and *S*. Dublin show a

higher predisposition for bacteremia in humans [33]. After gaining entry to the bloodstream, *Salmonella* get metastasize to different organs and cause focal suppurative infection. In sickle cell anemic patients a common finding as a result of NTS is osteomyelitis [34]. Less frequent occurrence of meningitis has been observed specially in infants [35]. Despite of antibiotic therapy, patients may develop rapid neurological deterioration. Other feared lethal complications include development of endarteritis [36], endocarditis [37], meningitis [38], lung infestations [39], appendicitis [40], pneumonia [41], bone and joint defects [15] and cerebral abscess [42].

#### **5. Multiple drug resistance**

In current scenario, there has been an extensive increase in documentation of antimicrobial resistance in NTS. Multiple drug resistance (MDR) is the antimicrobial resistance shown by the microorganism to at least three different groups of antimicrobials. Some *Salmonella* strains are characterized by carrying several antimicrobial resistance. The possibility of having MDR in bacteria is due to the presence of several different resistance genes or a single resistance gene that shows resistance to more than one antibiotic. Some important factors that could cause MDR in microorganisms include selective pressures, proliferation of multiple resistant clones, and inability to detect emerging phenotypes. The overuse or misuse of antimicrobials for the treatment of human disease, in agriculture, and in-home disinfectants comes under selective pressure [43]. The development of the antimicrobial resistance in bacteria is as a result of the genetic modifications of a microorganism for its own survival either spontaneously or acquired. In spontaneous mutation, a genetic modification occurs naturally which helps to survive from the lethal effects of antimicrobials. The reason behind the occurrence of spontaneous mutations is unknown, but the exposure to the antimicrobials may provide selective pressure for antimicrobial resistance [44]. Acquired resistance eventuate from gene transfer from other bacteria [45]. High resistance rate have been reported from *S.* Typhimurium DT104, resistant to five antimicrobial agents i.e. ampicillin, chloramphenicol, streptomycin, sulphonamide, and tetracycline [46]. Resistance to some extended spectrum antibiotics like cephalosporins and fluoroquinolones have been increasingly reported [47]. The emergence of *S*. Choleraesuis resistance to multiple antibiotics including ciprofloxacin has posed serious public health concerns [48].

Bacteria develop MDR by three different mechanisms. In first mechanism of resistance, the bacteria are known to produce certain specific proteins such as hydrolytic enzymes, which destroy the antimicrobials present in their surroundings. An example to this is penicillin resistance, where *Salmonella* produces β-lactamases enzymes which cleave the β-lactam ring of active penicillin and convert it into its inactive form [49]. The second mechanism of resistance is the presence of an active efflux pump system in the cell which actively pumps out the antimicrobials before they become effective [45]. *Salmonella* have energy-dependent efflux pumps for tetracycline and chloramphenicol which inhibit protein synthesis in bacteria by binding to tRNA to the A-site of the 30S subunit of the ribosome [50]. The third mechanism of resistance is called as the receptor modification in which the bacteria tends to chemically modify or mutate the target of the antimicrobial agent. For example vancomycin is the antibiotic which binds with D-Ala-D-Ala on the cell wall and inhibits the peptidoglycan synthesis of the cell wall of bacteria. But vancomycin-resistant enterococcus mutates its terminal peptide to D-Ala-D-Lac that has a lower affinity for vancomycin [45]. The mechanism of action adopted by *Salmonella* for different antimicrobial classes has been enlisted in **Table 1**. Plasmid mediated

*Non-Typhoidal Salmonellosis: A Major Concern for Poultry Industry DOI: http://dx.doi.org/10.5772/intechopen.96400*


#### **Table 1.**

*Antimicrobial mechanisms of* Salmonella *for different antimicrobial class.*

resistance determinants (genes) to antimicrobials have been known to be responsible for the worldwide dissemination of several *Salmonella* serotypes i.e. Enteritidis, Heidelberg, Typhimurium, Infantis, Virchow, Kentucky. The most common genes found in poultry and its meat products are β-lactamases, *CTX-M* (*CTX-M-1, −2, −9* and *− 15*), *TEM-52*, *AmpC-type CMY-2*. The transmission of these genes is associated with diverse plasmid families such as Incl l (*bla*CTX-M-1*, bla*TEM-52, *bla*CMY-2), Incl A/C (*bla*CMY-2), Incl H12 (*bla*CTX-M-2, *bla*CTX-M-9). Plasmid mediated quinolone resistance is governed by *QnrB2*, *QnrB19, QnrS1* genes. The genes mediating R-type ACSSuT in NTS are commonly clustered together in *Salmonella* genomic island 1 (SGI-1), a chromosomal genetic element.
