Summary: Yersinia pseudo-tuberculosis mitogen
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Yersinia pseudotuberculosis Edit Wikipedia article
Smith & Thal 1965
Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by Y. pseudotuberculosis. The bacterium is urease positive.
Yersinia scanned with electron micrograph
|Classification and external resources|
In humans, symptoms of Far East scarlet-like fever are similar to those of infection with Yersinia enterocolitica (fever and right-sided abdominal pain), except that the diarrheal component is often absent, which sometimes makes the resulting condition difficult to diagnose. Y. pseudotuberculosis infections can mimic appendicitis, especially in children and younger adults, and, in rare cases, the disease may cause skin complaints (erythema nodosum), joint stiffness and pain (reactive arthritis), or spread of bacteria to the blood (bacteremia).
Far East scarlet-like fever usually becomes apparent five to 10 days after exposure and typically lasts one to three weeks without treatment. In complex cases or those involving immunocompromised patients, antibiotics may be necessary for resolution; ampicillin, aminoglycosides, tetracycline, chloramphenicol, or a cephalosporin may all be effective.
The recently described syndrome "Izumi-fever" has been linked to infection with Y. pseudotuberculosis.
The symptoms of fever and abdominal pain mimicking appendicitis (actually from mesenteric lymphadenitis)  associated with Y. pseudotuberculosis infection are not typical of the diarrhea and vomiting from classical food poisoning incidents. Although Y. pseudotuberculosis is usually only able to colonize hosts by peripheral routes and cause serious disease in immunocompromised individuals, if this bacterium gains access to the blood stream, it has an LD50 comparable to Y. pestis at only 10 CFU.
Relationship to Y. pestis
Genetically, the pathogen causing plague, Y. pestis, is very similar to Y. pseudotuberculosis. The plague appears to have evolved from Y. pseudotuberculosis about 1500 to 20,000 years ago. A 2015 paper in Cell argued for an older divergence.
To facilitate attachment, invasion, and colonization of its host, this bacterium possesses many virulence factors. Superantigens, bacterial adhesions, and the actions of Yops (which are bacterial proteins once thought to be "Yersinia outer membrane proteins") that are encoded on the "[plasmid] for Yersinia virulence" – commonly known as the pYV – cause host pathogenesis and allow the bacteria to live parasitically.
The 70-kb pYV is critical to Yersinia's pathogenicity, since it contains many genes known to encode virulence factors and its loss gives avirulence of all Yersinia species. A 26-kb "core region" in the pYV contains the ysc genes, which regulate the expression and secretion of Yops. Many Ysc proteins also amalgamate to form a type-III secretory apparatus, which secretes many Yops into the host cell cytoplasm with the assistance of the "translocation apparatus", constructed of YopB and YopD. The core region also includes yopN, yopB, yopD, tyeA, lcrG, and lcrV, which also regulate Yops gene expression and help to translocate secretory Yops to the target cell. For example, YopN and TyeA are positioned as a plug on the apparatus so only their conformational change, induced by their interaction with certain host cell membrane proteins, will cause the unblocking of the secretory pathway. Secretion is regulated in this fashion so that proteins are not expelled into the extracellular matrix and elicit an immune response. Since this pathway gives secretion selectivity, it is a virulence factor.
In contrast to the ysc and yop genes listed above, the Yops that act directly on host cells to cause cytopathologic effects – "effector Yops" – are encoded by pYV genes external to this core region. The sole exception is LcrV, which is also known as the "versatile Yop" for its two roles as an effector Yop and as a regulatory Yop. The combined function of these effector Yops permits the bacteria to resist internalization by immune and intestinal cells and to evade the bactericidal actions of neutrophils and macrophages. Inside the bacterium, these Yops are bound by pYV-encoded Sycs (specific Yop chaperones), which prevent premature interaction with other proteins and guide the Yops to a type-III secretory apparatus. In addition to the Syc-Yop complex, Yops are also tagged for type III secretion either by the first 60nt in their corresponding mRNA transcript or by their corresponding first 20 N-terminal amino acids. LcrV, YopQ, YopE, YopT, YopH, YpkA, YopJ, YopM, and YadA are all secreted by the type-III secretory pathway. LcrV inhibits neutrophil chemotaxis and cytokine production, allowing Y. pseudotuberculosis to form large colonies without inducing systemic failure and, with YopQ, contributes to the translocation process by bringing YopB and YopD to the eukaryotic cell membrane for pore-formation. By causing actin filament depolymerisation, YopE, YopT, and YpkA resist endocytosis by intestinal cells and phagocytosis while giving cytotoxic changes in the host cell. YopT targets Rho GTPase, commonly named "RhoA", and uncouples it from the membrane, leaving it in an inactive RhoA-GDI (guanine nucleotide dissociation inhibitor)-bound state whereas YopE and YpkA convert Rho proteins to their inactive GDP-bound states by expressing GTPase activity. YpkA also catalyses serine autophosporylation, so it may have regulatory functions in Yersinia or undermine host cell immune response signal cascades since YpkA is targeted to the cytoplasmic side of the host cell membrane. YopH acts on host focal adhesion sites by dephosphorylating several phosphotyrosine residues on focal adhesion kinase (FAK) and the focal adhesion proteins paxillin and p130. Since FAK phosphorylation is involved in uptake of yersiniae as well as T cell and B cell responses to antigen-binding, YopH elicits antiphagocytic and other anti-immune effects. YopJ, which shares an operon with YpkA, "...interferes with the mitogen-activated protein (MAP) kinase activities of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase", leading to macrophage apoptosis. In addition, YopJ inhibits TNF-α release from many cell types, possibly through an inhibitory action on NF-κB, suppressing inflammation and the immune response. By secretion through a type III pathway and localization in the nucleus by a vesicle-associated, microtubule-dependent method, YopM may alter host cell growth by binding to RSK (ribosomal S6 kinase), which regulates cell cycle regulation genes. Interestingly, YadA has lost its adhesion, opsonisation-resisting, phagocytosis-resisting, and respiratory burst-resisting functions in Y. pseudotuberculosis due to a frameshift mutation by a single base-pair deletion in yadA in comparison to yadA in Y. enterocolitica, yet it still is secreted by type III secretion. The yop genes, yadA, ylpA, and the virC operon are considered the "Yop regulon" since they are coregulated by pYV-encoded VirF. virF is in turn thermoregulated. At 37 degrees Celsius, chromosomally encoded Ymo, which regulates DNA supercoiling around the virF gene, changes conformation, allowing for VirF expression, which then up-regulates the Yop regulon.
Y. pseudotuberculosis adheres strongly to intestinal cells via chromosomally encoded proteins so that Yop secretion may occur, to avoid being removed by peristalsis, and to invade target host cells. A transmembrane protein, Invasin, facilitates these functions by binding to host cell αβ1 integrins. Through this binding, the integrins cluster, thereby activating FAK, and causing a corresponding reorganization of the cytoskeleton. Subsequent internalization of bound bacteria occurs when the actin-depolymerising Yops are not being expressed. The protein encoded on the "attachment invasion locus" named Ail also bestows attachment and invasive abilities upon Yersiniae while interfering with the binding of complement on the bacterial surface. To increase binding specificity, the fibrillar pH6 antigen targets bacteria to target intestinal cells only when thermoinduced.
Certain strains of Yersinia pseudotuberculosis express a superantigenic exotoxin, YPM, or the Y. pseudotuberculosis-derived mitogen, from the chromosomal ypm gene. YPM specifically binds and causes the proliferation of T lymphocytes expressing the Vβ3, Vβ7, Vβ8, Vβ9, Vβ13.1, and Vβ13.2 variable regions  with CD4+ T cell preference, although activation of some CD8+ T cells occurs. This T cell expansion can cause splenomegaly coupled with IL-2 and IL-4 overproduction. Since administering anti-TNF-α and anti-IFN-γ monoclonal antibodies neutralizes YPM toxicity in vivo, these cytokines are largely responsible for the damage caused indirectly by the exotoxin. Strains that carry the exotoxin gene are rare in Western countries, where the disease, when at all apparent, manifests itself largely with minor symptoms, whereas more than 95% of strains from Far Eastern countries contain ypm and are correlated with Izumi fever and Kawasaki disease. Although the superantigen poses the greatest threat to host health, all virulence factors contribute to Y. pseudotuberculosis viability in vivo and define the bacterium’s pathogenic characteristics. Y. pseudotuberculosis can live extracellularly due to its formidable mechanisms of phagocytosis and opsonisation resistance through the expression of Yops and the type III pathway; yet, by limited pYV action, it can populate host cells, especially macrophages, intracellularly to further evade immune responses and be disseminated throughout the body.
crystal structure of yersinia pseudotuberculosis-derived mitogen (ypm)
Yersinia pseudotuberculosis-derived mitogens (YpM) are superantigens, which are able to excessively activate T cells by binding to the T cell receptor. Since YpM can activate large numbers of the T cell population, this leads the release of inflammatory cytokines.
Members of this family of Yersinia pseudotuberculosis mitogens adopt a sandwich structure consisting of 9 strands in two beta sheets, in a jelly-roll topology. YpM molecular weight is about 14 kDa. Structurally, it is unlike any other superantigen, but is remarkably similar to the tumour necrosis factor and viral capsid proteins. This suggests a possible evolutionary relationship.
Some highly homologous variants of YPM have been characterized, including YPMa, YPMb, and YPMc.
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|Wikispecies has information related to: Yersinia pseudotuberculosis|
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Yersinia pseudo-tuberculosis mitogen Provide feedback
Members of this family of Yersinia pseudo-tuberculosis mitogens adopt a sandwich structure consisting of nine strands in two beta sheets, in a jelly-roll topology. As with other super-antigens, they are able to excessively activate T cells by binding to the T cell receptor .
Donadini R, Liew CW, Kwan AH, Mackay JP, Fields BA; , Structure. 2004;12:145-156.: Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold. PUBMED:14725774 EPMC:14725774
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InterPro entry IPR015227
Members of this family of Yersinia pseudotuberculosis mitogens adopt a sandwich structure consisting of nine strands in two beta sheets, in a jelly-roll topology. As with other superantigens, they are able to excessively activate T cells by binding to the T cell receptor [PUBMED:14725774].
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the YpM domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...