YfdX: Difference between revisions

Typhoid fever is a disease that can be spread by contaminated food or water and causes symptoms of lasting fever, weakness, stomach pains, headache, loss of appetite, constipation and sometimes internal bleeding <ref name=chong>PMID: 28656014</ref>. S. Typhi it is an etiologic agent, the microbial toxin that causes disease in humans. S Typhi is a human restricted disease however, some higher primates can be infected experimentally (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). S. Typhi is 90% homologous to S Typhimurium but S. Typhimurium can infect both humans and primates (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). S. Typhi is unique for a couple of small reasons. First S. Typhi has a large region specific to it, Salmonella pathogenicity island 7 that encodes the viaB locus (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). This locus consists of ten genes related to the biosynthesis and export of Vi polysaccharides capsule (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). This involves circumventing Toll-Like Receptors mediated immune surveillance (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). Another area that is specific to S. Typhi is a small island with a locus encoding five genes (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).  These genes include three typhoid toxins components, a bacteriophage muramidase homolog controlling typhoid toxin secretions and a small gene of unknown function (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).

When a person is infected with typhoid it is spread through the intestinal tract the bloodstream. The reason this disease is so toxic is from <scene name='81/814058/Typhoid_toxin/9'>typhoid toxin</scene>, a unique factor produced by S. typhi (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). The toxin is a different type <scene name='81/814058/Ab_toxin/1'>AB toxin</scene> which means it is made up of one A subunit and 1 B subunit (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). Typhoid toxin has 2 types of A subunits and 1 B subunit. The A subunits are <scene name='81/814058/Ptla/1'>PltA</scene> and <scene name='81/814058/Cdtb/1'>CdtB</scene>, and the B subunit is <scene name='81/814058/Ptlb/1'>PltB</scene> (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). Research has shown that the toxin is made up of 1 molecule of each PltA and CdtB with <scene name='81/814058/5_molecules_of_ptlb/1'>5 molecules of PltB</scene> (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). The combination of Typhoid toxin subunits is what leads it to be very toxic. The typhoid toxin can bind to a wide variety of cells by attaching to certain types of proteins presents on the surface of many cells (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).  These proteins have a specific carbohydrate called glycan and typhoid toxin binds very well to this. Research has shown if there is a reduction in glycans leads to a reduction in typhoid toxin binding (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).  The PltB is thought to be responsible to the binding of the glycans because it has a pocket for the binding of glycans. Typhoid toxin primarily targets immune cells and the central nervous system, leading to the reason why the symptoms are so severe (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).

The two A subunits are enzymatic, and this is important because it shows molecular evolution and how these two separate toxins fused together and became one (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). Thus, leading to its incredible virulence because it’s becoming more complex and harder for organisms to deal with the infection. A similar toxin that has the similar structure of the two A enzymatic subunits is Anthrax toxin however, it has A subunits from two individual toxin complexes that have one A subunit (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)).   This means that the typhoid toxin is the first to be discovered of its kind. Along with the two enzymatic subunits becoming one it’s trafficking mechanism is also different from typical AB toxin (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). Typhoid toxin is exclusively produced in the intracellular infected cells, which in most cases is a vacuole in the epithelial lining of the intestines, leads to believe that the infected cells are apart of the export trafficking of typhoid toxin to extracellular milieu (Chong, A., Lee, S., Yang, Y. A., & Song, J. (2017)). This type of mechanism allows the typhoid toxin to be extremely virulent and spread so quickly.