S. Typhi is an enteric bacillus which belongs,to the genus Salmonella in the family Enterobacteriacaea and it is a multi–organs pathogen which inhibits the lymphatic tissues of the small intestine, liver, spleen, and blood stream of infected humans. S. Typhi has a mixture of features that make it an efficient pathogen. This species contains an endotoxin that is characteristic of Gram-negative organisms, as well as the virulence-enhancing Vi antigen. Many of the S. Typhi virulence factors are clustered in some areas of the chromosome known as Salmonella pathogenicity islands (SPI), such as adhesion, invasion, and toxin genes. A protein known as invasin that permits non-phagocytic cells is also produced and excreted by the bacterium., Where it is capable of intracellular living. The oxidative burst of leukocytes may also be inhibited, making innate immune reaction ineffective.
- S. Typhi-virulence factors -endotoxin
It was quite a long time before typhoid fever was differentiated from other febrile disorders. Pierre Louis was the first who used the word “ typhoid “ and give the classical picture of typhoid in 1829 and described in detail post-mortem finding, especially the enlargement and ulceration of peyer’s patches. However, he did not clearly differentiate between typhoid and typhus. In 1837, Gerhard was the first who clearly differentiate typhoid from typhus fever and William Budd described the contagious nature of the disease and Incriminated transmission of facially polluted water supplies in 1873 .
In 1873, William Budd, a physician in Bristol who was interested in cholera and intestinal fever, showed that typhoid fever could be transmitted by a particular toxin found in the excrement and that this propagation was responsible for the contamination of water by the feces of patients. Each case was linked to another anterior case, according to Budd. A significant number of doctors and scientists have attempted to discover the nature of the disease-causing microorganism and have experienced considerable difficulty in isolating the bacillus. It was Karl Joseph Eberth, Rudolf Virchow’s doctor and pupil, who discovered the bacillus in the abdominal lymph nodes and the spleen in 1879. In 1880 and 1881, he reported his findings. The genus ‘
2. Virulence factors of
Virulence factors in
2.1 Vi antigen
The capsular Vi antigen is a linear homopolymer of alpha 1–4 linked to galactose aminouronic acid which is variably acetylated at the C3 position. This antigen is believed to inhibit phagocytosis and complement C3 activation thus inhibiting non-specific opsonization, “ One of the main characteristics that distinguishes
2.2 The SPI-1, SPI-2 and type III secretion systems
Common to both typhoidal and NTS are two pathogenicity-island encoded type III secretion systems (T3SS): the SPI-1 and SPI-2 T3SS, which are essential for
2.3 Somatic O antigen (cell wall Ag or LPS)
The outer L-layer underlying the capsular material has the lipopolysaccharide (LPS) called the ‘0’ antigen. This’L’ layer also has certain proteins called outer membrane proteins (OMP) which are antigenic. These OMPs include both porin (OMP F and OMP C) and non-porin substances. Porins are pore-forming channels which help in solute uptake and non-porin proteins are structural proteins (Figure 2) . These antigens are highly immunogenic and there is a good antibody response to all these antigens in patients with typhoid fever.”. [24, 25]. The somatic antigens represent the side chains of repeating sugar unit projecting outwards from the lipopolysaccharide layer and the surface of the bacterial cell wall; they are hydrophilic and heat stable. It is used for serological diagnosis .
2.4 Flagella(H antigen)
Flagella, while contributing to virulence, are also important activators of innate immune responses via recognition of monomeric flagellin by TLR5 and NAIP receptors [27, 28], H antigen may occur in either or both of two forms, called phase 1 and phase 2. The organism tends to change from one phase to the other. H antigen also provides a useful epidemiologic tool with which to determine the source of infection and its mode of spread ; While most NTS display phase variation through the alternate expression of two genes of flagellin (fliC and fljB), most S. Typhi strains are monophasic, expressing FliC of the antigen H: d directly. Interestingly, some Indonesian S. Typhi strains transmit H: j, due to an in-frame deletion in fliC, a variant of H:d. , and/or are biphasic, expressing a plasmid-encoded FljB analogue of the H:z66 antigen , H:j and H:z66 antigenic variants are thought to have recently emerged during S. Typhi evolution , driven by immune selection in this high incidence region . This additional variation seems to play a role in
2.5 Fimbriae (adhesion protein) and pili
The significant adhesion factors for S. Typhi are fimbriae and pili. These elements of virulence are employed by S. Typhi during infection and host colonization for its various cellular interactions . The Operon Stg, one of the six Operons Fimbriae found in S. Typhi, But not S. Typhimurium has recently been shown to be involved in cellular invasion and in vitro destruction of epithelial cells . In addition, the STG operon was found to assist S. Typhi targets enterocytes more preferentially than M cells, which promotes S. Typhi By passing the Peyer patches, eludes the innate immune system .
2.6 Virulence plasmid
Unlike most bacteria that rely on endocytosis mediated by receptors in order to invade a target cell, S. Typhi uses a complex mechanism known as bacterial mediated endocytosis, in which bacterial proteins enter the host cell and control signaling cascades that regulate the trafficking of cytoskeletal membrane architecture and gene expression, both of which force endocytosis S. Typhi into the host [37, 38]. The target cell for
Biofilm cells manufacture proteinaceous substances that allows synergic growth and protection from possible harsh environments it may encounter [39, 40]. In the seventeenth horn, a Dutch scientist Van Leeuwenhoek was the first individual to discover biofilm cells which he described as “animacules” on his dental plaque. The biofilm development process is initiated with single cells attaching to a surface or to each other, this is then followed by the formation of clustered cells or microcolonies. Over time, the microcolonies are surrounded by a protective layer of protein-rich substances referred to as extracellular polymeric substances (EPS) . The development and genetic signaling pathways involved in a
Enea et al.  were found biofilm production by
2.9 Endotoxin of
Endotoxin is a big part of Gram-negative bacteria’s outer membrane (OM). Endotoxins have been found to play an important function in the pathogenicity of Gram-negative bacterial infections. It is a powerful mediator of a wide range of pathophysiological effects in humans, mainly in the gasterointestinal tracts. Therefore, these are also known as enterotoxins. These toxic behaviors, as well as many beneficial ones linked to immunostimulation, include lethal toxicity, pyrogenicity and tissue necrotizing activity . Endotoxins are high-molecular weight complexes, of lipopolysaccharides (LPS) which is the major component of bacterial cell wall . It’s a heat stable toxic substance released by gram negative bacteria’s after disruption of cell envelopes [43, 44]. The role of endotoxins in bacterial pathogenesis and their chemical characterization as lipopolysaccharide (LPS) have been studied earlier [45, 46]. Chemically, LPS consist of a hydrophilic polysaccharide covalently linked to a hydrophobic lipid portion which is termed as lipid A, which anchors the molecules in the outer membrane (OM) . Endotoxins play a major role in human disease states that created interest to investigate the pathogenicity of the producing bacteria . Lipopolysaccharide found to be an important activator for the activation of immune system that leads to non- specific inflammatory immune response .
According to above review we put highlights on the role of the
Conflict of interest
There is no ‘conflict of interest’ for this work.