*2.1.1.1 Mannose-sensitive Type I fimbriae (Fim)*

Mannose-sensitive Type I fimbriae (Fim) are encoded by the *fim ACDHIFZYW* operon and bind to D-mannose-containing receptors on host cell surface as well as the glycoprotein laminin of the extracellular matrix [24]. Type I fimbriae promoted bacterial attachment to epithelial cells, facilitated the invasion of HEp-2 cells and HeLa cells and the colonization of the gut mucosa in chicken, mouse, rat and swine [25, 26]. An immunization experiment using purified Fim protein led to the protection of laying hens against egg contamination and colonization of the reproductive organs by *S. enteritidis* [27]. FimA, FimF, and FimH are necessary for the assembly of Type 1 fimbriae on *S. typhimurium* [24]. Differently, *STM0551* gene plays a negative regulatory role in the regulation of type 1 fimbriae in *S. typhimurium* [28].

### *2.1.1.2 Plasmid-encoded fimbriae (Pef)*

Plasmid-encoded fimbriae (Pef) participate in the attachment of bacteria to the surface of murine small intestine and are necessary for fluid production in the infant mouse similar to the observation with the fimbriae of enterotoxigenic *Escherichia coli* and *Vibrio cholerae* [29]. Expression of *pef* gene is regulated by DNA methylation [30]. Purified Pef specifically binds the trisaccharide Galβ1- 4(Fucα1-3) GlcNAc (also known as the Lewis X blood group antigen or Lex ), which are preponderant on the surface of human erythrocytes, skin epithelium and mucosal surfaces [31].

## *2.1.1.3 Long polar fimbriae (Lpf)*

Long polar fimbriae (Lpf) encoded by the *lpfABCDE* fimbrial operon is involved in the colonization of murine Peyer's patches by mediating adherence to M cells, a preferred port of entry for *Salmonella* in mice [32]. Mutation of the *lpfC* gene which encodes the fimbrial outer membrane usher attenuated the virulence of *Salmonella typhimurium* in orally exposed mice as shown by a 5-fold increase in the number of organisms needed to kill 50% of test animals (i.e., LD50) when compared to the wild type organism. Lpf is also involved in the early stages of biofilm formation on host epithelial cells [33] and participate in intestinal persistence in mice [34].

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for mice [39].

**Table 1.**

*attachment.*

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

**Virulence genes Location\* Functions**

*BcfABCDEFGH* Chromosome Contribute to long-term intestinal carriage and bovine colonization *csgABCDEFG* Chromosome Curlin subunit; assembly and transport component in curli

*lpfABCDE* Chromosome Biofilm formation, contribute to long-term intestinal carriage *misL* SPI-3 An extracellular matrix adhesion involved in intestinal colonization *pefA* Plasmid Adhesion to crypt epithelial cells; induction of proinflammatory response

*fimCDFHIWYZ* Chromosome Adhesion to epithelial cells; biofilm formation

*SafC* Chromosome Salmonella atypical fimbria outer membrane usher

*stfACDEFG* Chromosome Not required for long-term intestinal carriage of mice

*sthABD* Chromosome Outer membrane fimbrial usher. Putative fimbrial subunit and chaperone protein

*STM0551* Chromosome Downregulates fimbrae protein expression and acts as a negative regulator of virulence

*StdB* Chromosome Contribute to long-term intestinal carriage

*StiABC* Chromosome Putative fimbrial subunit/usher/chaparone

*hofBC* Chromosome Type IV pilin biogenesis protein

*ppdD* Chromosome Putative major pilin subunit

*ShdA* CS54 Outer membrane

*STM4595* Chromosome Unknown function *\*SPI-3 and CS54 are genomic islands on Salmonella chromosome.*

production; DNA-binding transcriptional regulator

Lpf synthesis is regulated by an on–off switch mechanism (phase variation) to

*Location and function of the major proteins and virulence determinants contributing to Salmonella* 

Thin aggregative fimbriae also known as curli [36] with the designation Agf/ Csg, are encoded by the *agf/csgBAC* gene cluster [37]. The thin aggregative fimbriae for Enteritidis which is known as SEF 17 is responsible not only for the auto-aggregative phenotype of the bacteria, but for fibronectin binding [38] and has been shown *in vitro* to bind immortalized small intestinal epithelial cells from mice [36]. Mutation in *agfB* resulted in a 3- to 5-fold increase in the oral LD50 of Typhimurium

Bovine colonization factor (Bcf) is encoded by genes in the *bcf* gene cluster. The fimbrial usher protein encoded by *bcfC* is required for colonization of bovine but not murine Peyer's patches in oral infection models of calves and mice [40]. The *bcf* gene together with five other fimbrial operons—*lpf*, *stb*, *stc*, *std*, and *sth*—are reported to be required for long-term intestinal carriage of Typhimurium in geneti-

avoid host immune responses [35].

*2.1.1.5 Bovine colonization factor (Bcf)*

cally resistant mice [34].

*2.1.1.4 Thin aggregative fimbriae*


#### **Table 1.**

*Microorganisms*

ous environment within the host.

experimentally investigated [23] are outlined below.

*2.1.1.1 Mannose-sensitive Type I fimbriae (Fim)*

*2.1.1.2 Plasmid-encoded fimbriae (Pef)*

mucosal surfaces [31].

*2.1.1.3 Long polar fimbriae (Lpf)*

*2.1.1 Fimbrial adhesins*

contributing to colonization of a broad range of host species and adaptation to vari-

Fimbriae, also known as pili, are thin, filamentous appendages protruding on the bacterial surface and consist of polymerized aggregates of small molecular weight monomers of the fimbrin protein [16]. Characteristically, fimbriae mediate the initial attachment of Gram-negative bacterial pathogens to host cells and surfaces [17]. In *Salmonella*, the initial contact results in relatively weak adherence of the bacteria to intestinal epithelial cells but soon induces *de novo* bacterial protein synthesis which increases the strength and intimacy of the attachment [18]. This process is also accompanied by the development and assembly of a unique secretion apparatus called the Type 3 Secretion System (T3SS) which is required for *Salmonella* to invade epithelial cells [19]. The chromosome of *S. typhimurium* contains 13 fimbrial operons, *afg* (*csg*), *bcf*, *fim*, *lpf*, *pef*, *saf*, *stb*, *stc*, *std*, *stf*, *sth*, *sti*, and *stj* [20–22] (**Table 1** and **Figure 1**). Eight types of fimbriae which have been

Mannose-sensitive Type I fimbriae (Fim) are encoded by the *fim ACDHIFZYW* operon and bind to D-mannose-containing receptors on host cell surface as well as the glycoprotein laminin of the extracellular matrix [24]. Type I fimbriae promoted bacterial attachment to epithelial cells, facilitated the invasion of HEp-2 cells and HeLa cells and the colonization of the gut mucosa in chicken, mouse, rat and swine [25, 26]. An immunization experiment using purified Fim protein led to the protection of laying hens against egg contamination and colonization of the reproductive organs by *S. enteritidis* [27]. FimA, FimF, and FimH are necessary for the assembly of Type 1 fimbriae on *S. typhimurium* [24]. Differently, *STM0551* gene plays a negative regulatory role in the regulation of type 1 fimbriae in *S. typhimurium* [28].

Plasmid-encoded fimbriae (Pef) participate in the attachment of bacteria to the surface of murine small intestine and are necessary for fluid production in the infant mouse similar to the observation with the fimbriae of enterotoxigenic *Escherichia coli* and *Vibrio cholerae* [29]. Expression of *pef* gene is regulated by DNA methylation [30]. Purified Pef specifically binds the trisaccharide Galβ1- 4(Fucα1-3) GlcNAc (also known as the Lewis X blood group antigen or Lex

are preponderant on the surface of human erythrocytes, skin epithelium and

Long polar fimbriae (Lpf) encoded by the *lpfABCDE* fimbrial operon is involved in the colonization of murine Peyer's patches by mediating adherence to M cells, a preferred port of entry for *Salmonella* in mice [32]. Mutation of the *lpfC* gene which encodes the fimbrial outer membrane usher attenuated the virulence of *Salmonella typhimurium* in orally exposed mice as shown by a 5-fold increase in the number of organisms needed to kill 50% of test animals (i.e., LD50) when compared to the wild type organism. Lpf is also involved in the early stages of biofilm formation on host epithelial cells [33] and participate in intestinal persistence in mice [34].

), which

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*Location and function of the major proteins and virulence determinants contributing to Salmonella attachment.*

Lpf synthesis is regulated by an on–off switch mechanism (phase variation) to avoid host immune responses [35].

#### *2.1.1.4 Thin aggregative fimbriae*

Thin aggregative fimbriae also known as curli [36] with the designation Agf/ Csg, are encoded by the *agf/csgBAC* gene cluster [37]. The thin aggregative fimbriae for Enteritidis which is known as SEF 17 is responsible not only for the auto-aggregative phenotype of the bacteria, but for fibronectin binding [38] and has been shown *in vitro* to bind immortalized small intestinal epithelial cells from mice [36]. Mutation in *agfB* resulted in a 3- to 5-fold increase in the oral LD50 of Typhimurium for mice [39].

#### *2.1.1.5 Bovine colonization factor (Bcf)*

Bovine colonization factor (Bcf) is encoded by genes in the *bcf* gene cluster. The fimbrial usher protein encoded by *bcfC* is required for colonization of bovine but not murine Peyer's patches in oral infection models of calves and mice [40]. The *bcf* gene together with five other fimbrial operons—*lpf*, *stb*, *stc*, *std*, and *sth*—are reported to be required for long-term intestinal carriage of Typhimurium in genetically resistant mice [34].
