View source for Yersinia pseudotuberculosis

{{Short description|Species of bacterium}}
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{{Infobox medical condition (new)
| name            = Yersinia pseudotuberculosis
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| image           = Yersinia pestis scanned with electron micrograph.jpg
| caption         = Yersinia scanned with electron micrograph
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| field           = [[Infectious disease (medical speciality)|Infectious disease]]
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{{Speciesbox
| image =
| image_caption =
| genus = Yersinia
| species = pseudotuberculosis
| authority = (Pfeiffer 1889)<br />Smith &amp; Thal 1965
}}

'''''Yersinia pseudotuberculosis''''' is a [[Gram-negative]] [[bacterium]] that causes [[Far East scarlet-like fever]] in humans, who occasionally get infected [[zoonosis|zoonotically]], most often through the food-borne route.<ref name=Sherris>{{cite book | editor = Ryan KJ | editor2 = Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref> Animals are also infected by ''Y. pseudotuberculosis''. The bacterium is [[urease]] positive.

==Pathogenesis==
In animals, ''Y. pseudotuberculosis'' can cause [[tuberculosis]]-like symptoms, including localized tissue [[necrosis]] and [[granulomas]] in the [[spleen]], [[liver]], and [[lymph nodes]].

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''.<ref>{{cite web | author=Jani, Asim| year=2003| title=Pseudotuberculosis (Yersina) | url=http://www.emedicine.com/med/topic1947.htm | access-date=2006-03-04}}</ref>

The symptoms of fever and abdominal pain mimicking appendicitis (actually from mesenteric lymphadenitis) <ref name="C">{{cite book |last1=Carnoy |first1=C. |first2=N. |last2=Lemaitre |first3=M. |last3=Simonet |chapter=The superantigenic toxin of Yersinia pseudotuberculosis |editor-first=Daniel |editor-last=Ladant |editor2-first=Joseph E. |editor2-last=Alouf |editor3-first=Michel R. |editor3-last=Popoff |title=The Comprehensive Sourcebook of Bacterial Protein Toxins |chapter-url=https://books.google.com/books?id=gFol3jKI03EC&pg=PA862 |date=2005 |publisher=Academic Press |isbn=978-0-08-045698-0 |pages=862–871}}</ref><ref name="D">{{cite book |last1=Robins-Browne |first1=R. |first2=E. |last2=Hartland |chapter=Yersinia species |editor-first=Marianne D. |editor-last=Miliotis |editor2-first=Jeffrey W. |editor2-last=Bier |title=International Handbook of Foodborne Pathogens |chapter-url=https://books.google.com/books?id=sbwCpA-r9EQC&pg=PA323 |date=2003 |publisher=CRC Press |isbn=978-0-203-91206-5 |pages=323–355}}</ref><ref name="E">{{cite book |last=Lindler |first=L. |chapter=Virulence plasmids of ''Yersinia'': characteristics and comparison |editor-first=B.E. |editor-last=Funnell |editor2-first=G.J. |editor2-last=Phillips |title=Plasmid biology |publisher=ASM Press |year=2004 |isbn=978-1555812652  |pages=423–437 }}</ref> 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 LD<sub>50</sub> comparable to ''[[Y. pestis]]'' at only 10 CFU.<ref name="F">{{cite journal |author=Brubaker RR |title=The Vwa+ virulence factor of yersiniae: the molecular basis of the attendant nutritional requirement for Ca++ |journal=Rev. Infect. Dis. |volume=5 |issue=Suppl 4 |pages=S748–58 |year=1983 |pmid=6195719 |doi=10.1093/clinids/5.supplement_4.s748}}</ref>

==Relationship to ''Y. pestis''==
Genetically, the pathogen causing [[Plague (disease)|plague]], ''[[Yersinia pestis|Y. pestis]]'', is very similar to ''Y. pseudotuberculosis''. The plague appears to have diverged from ''Y. pseudotuberculosis'' relatively recently - about 1,500 to 20,000 years ago, and shortly before the first historically recorded outbreaks in humans.<ref>{{cite journal |author=Achtman, M. |author2=Zurth, K. |author3=Morelli, G. |author4=Torrea, G. |author5=Guiyoule, A. |author6=Carniel, E.|title=''Yersinia pestis'', the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis|journal=Proc. Natl. Acad. Sci. U.S.A. |date=23 November 1999 |volume=96 |issue=24 |pages=14043–8 |doi=10.1073/pnas.96.24.14043 |pmid=10570195 |pmc=24187|bibcode=1999PNAS...9614043A |doi-access=free }}</ref> A 2015 paper in [[Cell (journal)|Cell]] argued for a divergence around 6,000 years ago.<ref>{{Cite journal | url= | doi=10.1016/j.cell.2015.10.009| pmid=26496604| pmc=4644222| title=Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago| journal=Cell| volume=163| issue=3| pages=571–582| year=2015| last1=Rasmussen| first1=Simon| last2=Allentoft| first2=Morten&nbsp;Erik| last3=Nielsen| first3=Kasper| last4=Orlando| first4=Ludovic| last5=Sikora| first5=Martin| last6=Sjögren| first6=Karl-Göran| last7=Pedersen| first7=Anders&nbsp;Gorm| last8=Schubert| first8=Mikkel| last9=Van&nbsp;Dam| first9=Alex| last10=Kapel| first10=Christian&nbsp;Moliin&nbsp;Outzen| last11=Nielsen| first11=Henrik&nbsp;Bjørn| last12=Brunak| first12=Søren| last13=Avetisyan| first13=Pavel| last14=Epimakhov| first14=Andrey| last15=Khalyapin| first15=Mikhail&nbsp;Viktorovich| last16=Gnuni| first16=Artak| last17=Kriiska| first17=Aivar| last18=Lasak| first18=Irena| last19=Metspalu| first19=Mait| last20=Moiseyev| first20=Vyacheslav| last21=Gromov| first21=Andrei| last22=Pokutta| first22=Dalia| last23=Saag| first23=Lehti| last24=Varul| first24=Liivi| last25=Yepiskoposyan| first25=Levon| last26=Sicheritz-Pontén| first26=Thomas| last27=Foley| first27=Robert&nbsp;A.| last28=Lahr| first28=Marta&nbsp;Mirazón| last29=Nielsen| first29=Rasmus| last30=Kristiansen| first30=Kristian| display-authors=29}}</ref> These modern estimates differ dramatically from earlier suggestions in popular scientific literature which claimed that ''Y. pestis'' evolved in rodents "millions of years ago."<ref>''"The disease started millions of years ago in rodents in the Himalayan foothills..."'' {{cite book|last1=Karlen|first1=Arno|title=Man and Microbes: Disease and Plagues in History and Modern Times|date=22 May 1996|page=76|isbn=9780684822709|publisher=Simon & Schuster}}</ref>

==Virulence factors==
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.

===pYV===
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.<ref name="F"/>  A 26-kb "core region" in the pYV contains the ''ysc'' genes, which regulate the expression and secretion of Yops.<ref name="E"/>  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.<ref name="G">{{cite journal |vauthors=Iriarte M, Cornelis GR |title=Identification of SycN, YscX, and YscY, three new elements of the ''Yersinia'' yop virulon |journal=J. Bacteriol. |volume=181 |issue=2 |pages=675–80 |year=1999 |doi=10.1128/JB.181.2.675-680.1999 |pmid=9882687 |pmc=93427 |url=}}</ref><ref name="H">{{cite journal |vauthors=Cornelis GR, Boland A, Boyd AP, Geuijen C, Iriarte M, Neyt C, Sory MP, Stainier I |title=The virulence plasmid of ''Yersinia'', an antihost genome |journal=Microbiol. Mol. Biol. Rev. |volume=62 |issue=4 |pages=1315–52 |year=1998 |pmid=9841674 |pmc=98948 |url=|doi=10.1128/MMBR.62.4.1315-1352.1998}}</ref>  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.<ref name="E"/>  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.<ref name="E"/><ref name="J">{{cite journal |vauthors=Lee VT, Tam C, Schneewind O |title=LcrV, a substrate for ''Yersinia enterocolitica'' type III secretion, is required for toxin targeting into the cytosol of HeLa cells |journal=J. Biol. Chem. |volume=275 |issue=47 |pages=36869–75 |year=2000 |pmid=10930402 |doi=10.1074/jbc.M002467200 |doi-access=free }}</ref>  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.

===Effector Yops===
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.<ref name="E"/> 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.<ref name="E"/>  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.<ref name="H"/>  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]].<ref name="D"/>
LcrV, YopQ, YopE, YopT, YopH, YpkA, YopJ, YopM, and YadA are all secreted by the type-III secretory pathway.<ref name="D"/><ref name="E"/><ref name="J"/>  LcrV inhibits neutrophil [[chemotaxis]] and [[cytokine]] production, allowing ''Y. pseudotuberculosis'' to form large colonies without inducing systemic failure<ref name="J"/> and, with YopQ, contributes to the translocation process by bringing YopB and YopD to the eukaryotic [[cell membrane]] for pore-formation.<ref name="D"/><ref name="K">{{cite journal |vauthors=Zumbihl R, Aepfelbacher M, Andor A, Jacobi CA, Ruckdeschel K, Rouot B, Heesemann J |title=The cytotoxin YopT of ''Yersinia enterocolitica'' induces modification and cellular redistribution of the small GTP-binding protein RhoA |journal=J. Biol. Chem. |volume=274 |issue=41 |pages=29289–93 |year=1999 |pmid=10506187 |doi=10.1074/jbc.274.41.29289|doi-access=free }}</ref>  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<ref name="L">{{cite journal |vauthors=Persson C, Carballeira N, Wolf-Watz H, Fällman M |title=The PTPase YopH inhibits uptake of ''Yersinia'', tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions |journal=EMBO J. |volume=16 |issue=9 |pages=2307–18 |year=1997 |pmid=9171345 |pmc=1169832 |doi=10.1093/emboj/16.9.2307 }}</ref> whereas YopE and YpkA convert Rho proteins to their inactive GDP-bound states by expressing GTPase activity.<ref name="J"/>  YpkA also catalyses [[serine]] autophosphorylation, so it may have regulatory functions in ''Yersinia''<ref name="O">{{cite journal |vauthors=Håkansson S, Galyov EE, Rosqvist R, Wolf-Watz H |title=The ''Yersinia'' YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane |journal=Mol. Microbiol. |volume=20 |issue=3 |pages=593–603 |year=1996 |pmid=8736538 |doi=10.1046/j.1365-2958.1996.5251051.x|s2cid=46632209 }}</ref> or undermine host cell immune response signal cascades since YpkA is targeted to the cytoplasmic side of the host cell membrane.<ref name="P">{{cite journal |vauthors=Ruckdeschel K, Machold J, Roggenkamp A, Schubert S, Pierre J, Zumbihl R, Liautard JP, Heesemann J, Rouot B |title=''Yersinia enterocolitica'' promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production |journal=J. Biol. Chem. |volume=272 |issue=25 |pages=15920–7 |year=1997 |pmid=9188492 |doi=10.1074/jbc.272.25.15920|doi-access=free }}</ref>  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.<ref name="M">{{cite journal |vauthors=Alrutz MA, Isberg RR |title=Involvement of focal adhesion kinase in invasin-mediated uptake |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=23 |pages=13658–63 |year=1998 |pmid=9811856 |pmc=24875 |doi=10.1073/pnas.95.23.13658|bibcode=1998PNAS...9513658A |doi-access=free }}</ref>  Since FAK phosphorylation is involved in uptake of yersiniae<ref name="N">{{cite journal |vauthors=Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H |title=A secreted protein kinase of ''Yersinia pseudotuberculosis'' is an indispensable virulence determinant |journal=Nature |volume=361 |issue=6414 |pages=730–2 |year=1993 |pmid=8441468 |doi=10.1038/361730a0 |bibcode=1993Natur.361..730G |s2cid=4347737 }}</ref> as well as [[T cell]] and [[B cell]] responses to antigen-binding,<ref name="J"/> 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",<ref name="Q">{{cite journal |vauthors=Boland A, Cornelis GR |title=Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during ''Yersinia'' infection |journal=Infect. Immun. |volume=66 |issue=5 |pages=1878–84 |year=1998 |doi=10.1128/IAI.66.5.1878-1884.1998 |pmid=9573064 |pmc=108138 |url=}}</ref> leading to macrophage [[apoptosis]].<ref name="D"/>  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.<ref name="R">{{cite journal |vauthors=Skurnik M, el Tahir Y, Saarinen M, Jalkanen S, Toivanen P |title=YadA mediates specific binding of enteropathogenic ''Yersinia enterocolitica'' to human intestinal submucosa |journal=Infect. Immun. |volume=62 |issue=4 |pages=1252–61 |year=1994 |doi=10.1128/iai.62.4.1252-1261.1994 |pmid=8132332 |pmc=186266 |url=}}</ref>  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.<ref name="J"/>  YadA has lost its adhesion,<ref name="S">{{cite journal |vauthors=China B, Sory MP, N'Guyen BT, De Bruyere M, Cornelis GR |title=Role of the YadA protein in prevention of opsonization of ''Yersinia enterocolitica'' by C3b molecules |journal=Infect. Immun. |volume=61 |issue=8 |pages=3129–36 |year=1993 |doi=10.1128/iai.61.8.3129-3136.1993 |pmid=8335343 |pmc=280979 |url=}}</ref> [[opsonisation]]-resisting, phagocytosis-resisting, and [[respiratory burst]]-resisting functions<ref name="T">{{cite journal |vauthors=China B, N'Guyen BT, de Bruyere M, Cornelis GR |title=Role of YadA in resistance of ''Yersinia enterocolitica'' to phagocytosis by human polymorphonuclear leukocytes |journal=Infect. Immun. |volume=62 |issue=4 |pages=1275–81 |year=1994 |doi=10.1128/iai.62.4.1275-1281.1994 |pmid=8132334 |pmc=186269 |url=}}</ref><ref name="U">{{cite journal |vauthors=Han YW, Miller VL |title=Reevaluation of the virulence phenotype of the inv yadA double mutants of ''Yersinia pseudotuberculosis'' |journal=Infect. Immun. |volume=65 |issue=1 |pages=327–30 |year=1997 |doi=10.1128/iai.65.1.327-330.1997 |pmid=8975933 |pmc=174597 |url=}}</ref> 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.<ref name="V">{{cite journal |vauthors=Cornelis GR, Sluiters C, Delor I, Geib D, Kaniga K, Lambert de Rouvroit C, Sory MP, Vanooteghem JC, Michiels T |title=ymoA, a ''Yersinia enterocolitica'' chromosomal gene modulating the expression of virulence functions |journal=Mol. Microbiol. |volume=5 |issue=5 |pages=1023–34 |year=1991 |pmid=1956283 |doi=10.1111/j.1365-2958.1991.tb01875.x|s2cid=40096958 }}</ref>  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.<ref name="W">{{cite journal |vauthors=Isberg RR, Van Nhieu GT |title=Two mammalian cell internalization strategies used by pathogenic bacteria |journal=Annu. Rev. Genet. |volume=28 |pages=395–422 |year=1994 |pmid=7893133 |doi=10.1146/annurev.ge.28.120194.002143 }}</ref>

===Adhesion===
''Y. pseudotuberculosis'' adheres strongly to intestinal cells via chromosomally encoded proteins<ref name="D"/> 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]].<ref name="X">{{Cite journal |last=Miller |first=V. |year=1992 |title=''Yersinia'' invasion genes and their products |url=https://archive.org/details/sim_american-society-for-microbiology-asm-news_1992-01_58_1/page/n31 |journal=ASM News |volume=58 |pages=26–33}}</ref>  Through this binding, the integrins cluster, thereby activating FAK, and causing a corresponding reorganization of the cytoskeleton.<ref name="D"/><ref name="X" />  Subsequent internalization of bound bacteria occurs when the actin-depolymerising Yops are not being expressed.<ref name="J"/>  The protein encoded on the "attachment invasion locus" named Ail also bestows attachment and invasive abilities upon Yersiniae<ref name="Y">{{cite journal |vauthors=Bliska JB, Falkow S |title=Bacterial resistance to complement killing mediated by the Ail protein of ''Yersinia enterocolitica'' |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=8 |pages=3561–5 |year=1992 |pmid=1565652 |pmc=48908 |doi=10.1073/pnas.89.8.3561|bibcode=1992PNAS...89.3561B |doi-access=free }}</ref> while interfering with the binding of complement on the bacterial surface.<ref name="Z">{{cite journal |vauthors=Lindler LE, Tall BD |title=''Yersinia pestis'' pH 6 antigen forms fimbriae and is induced by intracellular association with macrophages |journal=Mol. Microbiol. |volume=8 |issue=2 |pages=311–24 |year=1993 |pmid=8100346 |doi=10.1111/j.1365-2958.1993.tb01575.x|s2cid=33124727 |url=https://zenodo.org/record/1230613 }}</ref>  To increase binding specificity, the fibrillar pH6 antigen targets bacteria to target intestinal cells only when thermoinduced.<ref name="AA">{{cite journal |vauthors=Miyoshi-Akiyama T, Fujimaki W, Yan XJ, Yagi J, Imanishi K, Kato H, Tomonari K, Uchiyama T |title=Identification of murine T cells reactive with the bacterial superantigen ''Yersinia pseudotuberculosis''-derived mitogen (YPM) and factors involved in YPM-induced toxicity in mice |journal=Microbiol. Immunol. |volume=41 |issue=4 |pages=345–52 |year=1997 |pmid=9159409 |doi=10.1111/j.1348-0421.1997.tb01211.x|doi-access=free }}</ref>

===Superantigens===
Certain strains of ''Yersinia pseudotuberculosis'' express a superantigenic exotoxin, YPM, or the ''Y. pseudotuberculosis''-derived mitogen, from the chromosomal ''ypm'' gene.<ref name="BB">{{cite journal |vauthors=Uchiyama T, Miyoshi-Akiyama T, Kato H, Fujimaki W, Imanishi K, Yan XJ |title=Superantigenic properties of a novel mitogenic substance produced by ''Yersinia pseudotuberculosis'' isolated from patients manifesting acute and systemic symptoms |journal=J. Immunol. |volume=151 |issue=8 |pages=4407–13 |year=1993 |pmid=8409410 |url=http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=8409410}}</ref>  YPM specifically binds and causes the proliferation of T lymphocytes expressing the Vβ3, Vβ7, Vβ8, Vβ9, Vβ13.1, and Vβ13.2 variable regions <ref name="CC">{{cite book |vauthors=Carnoy C, Loiez C, Faveeuw C, Grangette C, Desreumaux P, Simonet M |title=The Genus Yersinia |chapter=Impact of the Yersinia pseudotuberculosis -Derived Mitogen (YPM) on the Murine Immune System |volume=529 |pages=133–5 |pmid=12756744 |doi=10.1007/0-306-48416-1_26 |series=Advances in Experimental Medicine and Biology |date=2004 |isbn=978-0-306-47759-1 }}</ref> with [[CD4+ T cell]] preference, although activation of some CD8+ [[T cell]]s occurs.<ref name="C"/>  This T cell expansion can cause [[splenomegaly]] coupled with [[Interleukin 2|IL-2]] and [[Interleukin-4|IL-4]] overproduction.<ref name="DD">{{cite journal |vauthors=Yoshino K, Ramamurthy T, Nair GB, Fukushima H, Ohtomo Y, Takeda N, Kaneko S, Takeda T |title=Geographical heterogeneity between Far East and Europe in prevalence of ypm gene encoding the novel superantigen among ''Yersinia pseudotuberculosis'' strains |journal=J. Clin. Microbiol. |volume=33 |issue=12 |pages=3356–8 |year=1995 |doi=10.1128/jcm.33.12.3356-3358.1995 |pmid=8586739 |pmc=228710 |url=}}</ref>  Since administering anti-[[TNF-α]] and anti-[[IFN-γ]] monoclonal [[antibodies]] neutralizes YPM toxicity ''in vivo'',<ref name="BB"/> 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''<ref name="EE">{{cite journal |vauthors=Fukushima H, Matsuda Y, Seki R, Tsubokura M, Takeda N, Shubin FN, Paik IK, Zheng XB |title=Geographical heterogeneity between Far Eastern and Western countries in prevalence of the virulence plasmid, the superantigen ''Yersinia pseudotuberculosis''-derived mitogen, and the high-pathogenicity island among ''Yersinia pseudotuberculosis'' strains |journal=J. Clin. Microbiol. |volume=39 |issue=10 |pages=3541–7 |year=2001 |pmid=11574570 |pmc=88386 |doi=10.1128/JCM.39.10.3541-3547.2001 }}</ref> and are correlated with Izumi fever and [[Kawasaki disease]].<ref name="FF">{{cite journal |vauthors=Nikolova S, Najdenski H, Wesselinova D, Vesselinova A, Kazatchca D, Neikov P |title=Immunological and electronmicroscopic studies in pigs infected with ''Yersinia enterocolitica'' 0:3 |journal=Zentralbl. Bakteriol. |volume=286 |issue=4 |pages=503–10 |year=1997 |pmid=9440199 |doi=10.1016/s0934-8840(97)80053-9}}</ref>
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;<ref name="H"/> yet, by limited pYV action, it can populate host cells, especially macrophages, intracellularly to further evade immune responses and be disseminated throughout the body.<ref name="GG">{{cite journal |author=Smith MG |title=Destruction of bacteria on fresh meat by hot water |journal=Epidemiol. Infect. |volume=109 |issue=3 |pages=491–6 |year=1992 |pmid=1468533 |pmc=2271933 |doi=10.1017/s0950268800050482}}</ref>
{{Infobox protein family
| Symbol = YpM
| Name = YpM
| image = PDB 1pm4 EBI.jpg
| width = 
| caption = crystal structure of yersinia pseudotuberculosis-derived mitogen (ypm)
| Pfam = PF09144
| Pfam_clan =  
| InterPro = IPR015227
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 1pm4
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}

====Function<!--Yersinia pseudotuberculosis-derived mitogen redirects here-->====
''Yersinia pseudotuberculosis''-derived mitogens (YpM) are [[superantigens]], which are able to excessively activate [[T cell]]s by [[Binding (molecular)|binding]] to the T cell [[receptor (biochemistry)|receptor]]. Since YpM can activate large numbers of the T cell population, this leads the release of inflammatory [[cytokines]].

====Structure====
Members of this family of ''Yersinia pseudotuberculosis'' [[mitogen]]s adopt a sandwich [[secondary structure|structure]] consisting of 9 strands in two beta sheets, in a [[jelly roll fold]] 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.<ref name="pmid14725774">{{cite journal | vauthors = Donadini R, Liew CW, Kwan AH, Mackay JP, Fields BA | title = Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold | journal = Structure | volume = 12 | issue = 1 | pages = 145–56 |date=January 2004 | pmid = 14725774 | doi = 10.1016/j.str.2003.12.002| doi-access = free }}</ref>

====Subfamilies====
Some highly similar homologous variants of YPM have been characterized, including YPMa, YPMb, and YPMc.

=== small non-coding RNA ===
Numerous [[Bacterial small RNA|bacterial small non-coding RNAs]] have been identified to play regulatory functions. Some can regulate the virulence genes. 150 unannotated sRNAs were identified by sequencing of ''Y. pseudotuberculosis'' RNA libraries from bacteria grown at 26&nbsp;°C and 37&nbsp;°C, suggesting they may play a role in pathogenesis.<ref>{{Cite journal|last1=Koo|first1=Jovanka T.|last2=Alleyne|first2=Trevis M.|last3=Schiano|first3=Chelsea A.|last4=Jafari|first4=Nadereh|last5=Lathem|first5=Wyndham W.|date=2011-09-13|title=Global discovery of small RNAs in Yersinia pseudotuberculosis identifies Yersinia-specific small, noncoding RNAs required for virulence|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=37|pages=E709–717|doi=10.1073/pnas.1101655108|issn=1091-6490|pmid=21876162|pmc=3174644|doi-access=free}}</ref> By using single-molecule [[Fluorescence in situ hybridization|fluorescence in situ hybridisation]]  smFISH technique it was shown that the number of YSR35 RNA increased 2.5 times upon temperature shift from 25&nbsp;°C to 37&nbsp;°C.<ref>{{Cite journal|last1=Shepherd|first1=Douglas P.|last2=Li|first2=Nan|last3=Micheva-Viteva|first3=Sofiya N.|last4=Munsky|first4=Brian|last5=Hong-Geller|first5=Elizabeth|last6=Werner|first6=James H.|date=2013-05-21|title=Counting small RNA in pathogenic bacteria|journal=Analytical Chemistry|volume=85|issue=10|pages=4938–4943|doi=10.1021/ac303792p|issn=1520-6882|pmid=23577771|s2cid=18708152}}</ref> Another study uncovered that a temperature-induced global reprogramming of central metabolic functions are likely to support intestinal colonization of the pathogen. Environmentally controlled regulatory RNAs coordinate control of metabolism and virulence allowing rapid adaptation and high flexibility during life-style changes.<ref>{{Cite journal|last1=Nuss|first1=Aaron M.|last2=Heroven|first2=Ann Kathrin|last3=Waldmann|first3=Barbara|last4=Reinkensmeier|first4=Jan|last5=Jarek|first5=Michael|last6=Beckstette|first6=Michael|last7=Dersch|first7=Petra|date=2015-03-01|title=Transcriptomic profiling of Yersinia pseudotuberculosis reveals reprogramming of the Crp regulon by temperature and uncovers Crp as a master regulator of small RNAs|journal=PLOS Genetics|volume=11|issue=3|pages=e1005087|doi=10.1371/journal.pgen.1005087|issn=1553-7404|pmc=4376681|pmid=25816203 |doi-access=free }}</ref> High-throughput RNA structure probing identified many thermoresponsive RNA structures.<ref>{{Cite journal|last1=Righetti|first1=Francesco|last2=Nuss|first2=Aaron M.|last3=Twittenhoff|first3=Christian|last4=Beele|first4=Sascha|last5=Urban|first5=Kristina|last6=Will|first6=Sebastian|last7=Bernhart|first7=Stephan H.|last8=Stadler|first8=Peter F.|last9=Dersch|first9=Petra|date=2016-06-28|title=Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=113|issue=26|pages=7237–7242|doi=10.1073/pnas.1523004113|issn=1091-6490|pmc=4932938|pmid=27298343|doi-access=free}}</ref>

=== See also ===
* [[Intergenic lcrF RNA thermometer|Intergenic RNA thermometer]]

==References==
{{Reflist}}
{{InterPro content|IPR015227}}

== External links ==
{{Wikispecies}}
{{Medical resources
|  DiseasesDB     = 14237 
|  ICD10          = {{ICD10|A|04|8|a|4|0}}, A28.2 
|  ICD9           = 
|  ICDO           = 
|  OMIM           = 
|  MedlinePlus    = 
|  eMedicineSubj  = article 
|  eMedicineTopic = 226871 
|  MeshID         = D015012
}}
*[http://cmr.jcvi.org/tigr-scripts/CMR/GenomePage.cgi?org=ntyp05 Yersinia pseudotuberculosis genome]
*{{cite web |title=''Yersinia pseudotuberculosis'' |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=632 |id=632}}
*[http://bacdive.dsmz.de/index.php?search=5216&submit=Search Type strain of ''Yersinia pseudotuberculosis'' at Bac''Dive'' -  the Bacterial Diversity Metadatabase]

{{Gram-negative proteobacterial bacterial diseases}}
{{Taxonbar|from=Q139928}}
{{Authority control}}

[[Category:Yersinia|pseudotuberculosis]]
[[Category:Bacteria described in 1889]]
[[Category:Pathogenic bacteria]]