YfdX: Difference between revisions

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

<scene name='81/814058/Yfdx/6'>YfdX</scene> is a family protein that is encoded by several pathogenic bacteria such as Salmonella and E. coli. Particularly YfdX is encoded in Salmonella enterica serovar Typhi that causes a fatal disease called Typhoid Fever. Salmonella is a gram-negative bacterium that is excellent at infecting living organisms. They are fast replicating, mobile, and are armed with needle completes that can penetrate cells in the human digestive tract (“Salmonella Are Armed, Agile and Primed for Invasion.”). When Salmonella invade the epithelial cells lining the intestines it can survive and replicate inside membrane bond compartments called vacuoles (“Salmonella Are Armed, Agile and Primed for Invasion.”) The salmonella moves from cells to cell with a flagellum with in the intestine (“Salmonella Are Armed, Agile and Primed for Invasion.”).

 

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 <ref name=chong/>. S. Typhi is 90% homologous to S Typhimurium but S. Typhimurium can infect both humans and primates <ref name=chong/>. 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 <ref name=chong/>. This locus consists of ten genes related to the biosynthesis and export of Vi polysaccharides capsule <ref name=chong/>. This involves circumventing Toll-Like Receptors mediated immune surveillance <ref name=chong/>. Another area that is specific to S. Typhi is a small island with a locus encoding five genes <ref name=chong/>.  These genes include three typhoid toxins components, a bacteriophage muramidase homolog controlling typhoid toxin secretions and a small gene of unknown function <ref name=chong/>.

YfdX is a product of yfdXWUVE operon and is said to be under the control of <scene name='81/814058/Evga/1'>EvgA</scene>. EvgA come from the EvgAS. EvgAS is a two-component system that modulates drug resistance of E. coli by regulating the expression of the drug transporters <ref name=nishino>PMID: 12670992</ref>. EvgA research has shown that the toxin is made up of 1 molecule of each PltA and CdtB with 5 molecules of PltB (Nishino, K., Inazumi, Y., & Yamaguchi, A. (2003)). EvgA is the response regulator and modulates the expression of emrKY, which encodes a bile salt specific exporter and yhiUV which encodes a multidrug exporter (Nishino, K., Inazumi, Y., & Yamaguchi, A. (2003)). However, over expression of EvgA gives potential an acid resistant phenotype (Nishino, K., Inazumi, Y., & Yamaguchi, A. (2003)). The acid resistance is somewhat got in rid of by the deletion of ydeP, yhiE, or ydeO, genes induced by EvgA overexpression (Nishino, K., Inazumi, Y., & Yamaguchi, A. (2003)).  Along with EvgA most likely planning major role in tolerance to outside forces the yfdXWUVE operon does as well. The yfdXWUVE operon appears to encode proteins that enhance the ability of Salmonella to survive under acidic conditions (Toyota, Cory G., et al).  

YfdX weighs around 42kDa and is suggested to be a dimer in solution (Lee, Hye Seon, et al.). It has 10-186 residues from its total 199 amino acids (Lee, Hye Seon, et al.). It is composed of six α-helices, one 310-helix, and three β-strands. These arrange into three subdomains: a four helical bundle, and antiparallel β-sheet, and two helical bundles (Lee, Hye Seon, et al.). The importance of YfdX is that it plays a major role in Salmonella susceptibility to two β-lactam antibiotics, penicillin G and carbenicillin (Lee, Hye Seon, et al.). Without the YfdX protein the Salmonella virulence was enhanced. One specific type of YfdX protein is <scene name='81/814058/Sty3178/3'>STY3178</scene>. This comes from a multidrug resistant strain of Salmonella Typhi (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). The multidrug resistant strains of S. Typhi. have been reported to be resistant to antibiotics such as ciprofloxacin, rifampin, ampicillin, etc. (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). The structure of STY3178 was found in a study to be a well folded and predominately α-helical protein containing β-sheets elements (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). STY3178 is existing in a trimetric oligomerization state in solution. (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). Its ability to bind to antibiotics was found to demonstrate that different small antibiotics are capable of binding to STY3178 such as ciprofloxacin, rifampin, and ampicillin (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). Studies show that the binding of ciprofloxacin binding is stronger than rifampin flowed by ampicillin (Saha, P., Manna, C., Das, S., & Ghosh, M. (2016)). This is important to note because if a patient were to come down with typhoid fever and had the STY3178 protein it would be best to see which antibiotic would bind best to the STY3178 protein.  

 

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

== References ==  

 

 

 

Lee, Hye Seon, et al. “Structural and Physiological Exploration of Salmonella Typhi YfdX Uncovers Its Dual Function in Bacterial Antibiotic Stress and Virulence.” Frontiers in Microbiology, Frontiers Media S.A., 14 Jan. 2019, <references/>

Saha, P., Manna, C., Das, S., & Ghosh, M. (2016). Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi. Scientific reports, 6, 21305. doi:10.1038/srep21305<references/>