Editing Shigella

{{Short description|Genus of bacteria}}
{{About|the genus|the disease|shigellosis|the toxin that is produced by certain strains of ''Shigella'' and ''E. coli'' bacteria|Shiga toxin}}
{{Automatic taxobox
| image = Shigella_stool.jpg
| image_caption = [[micrograph|Photomicrograph]] of ''Shigella'' sp. in a stool specimen
| taxon = Shigella
| authority = Castellani & Chalmers 1919
| subdivision_ranks = Species
| subdivision =''[[Shigella boydii|S. boydii]]''<br />
''[[Shigella dysenteriae|S. dysenteriae]]''<br />
''[[Shigella flexneri|S. flexneri]]''<br />
''[[Shigella sonnei|S. sonnei]]''
}}

'''''Shigella''''' is a [[genus]] of [[bacteria]] that is [[Gram negative]], [[facultative aerobic organism|facultatively anaerobic]], [[Endospore|non–spore-forming]], nonmotile, [[Bacillus (shape)|rod shaped]], and is genetically nested within ''[[Escherichia]]''. The genus is named after [[Kiyoshi Shiga]], who discovered it in 1897.<ref>{{cite journal |last1=Yabuuchi |first1=Eiko |title=Bacillus dysentericus (sic) 1897 was the first taxonomic rather than Bacillus dysenteriae 1898 |journal=International Journal of Systematic and Evolutionary Microbiology |volume=52 |issue=Pt 3 |pages=1041 |year=2002 |pmid=12054222 |doi=10.1099/00207713-52-3-1041 |doi-access=free }}</ref>

''Shigella'' causes disease in [[primate]]s, but not in other mammals; it is the causative agent of human [[shigellosis]].<ref>{{cite book |title=Sherris medical microbiology: an introduction to infectious diseases |year=2004 |publisher=McGraw-Hill Professional Med/Tech |isbn=978-0-8385-8529-0 |edition=4th |editor1-last=Ryan |editor1-first=Kenneth James |editor2-last=Ray |editor2-first=C. George}}{{page needed|date=February 2012}}</ref> It is only naturally found in humans and gorillas.<ref>{{cite book |first1=Kathy |last1=Pond |year=2005 |chapter=Shigella |chapter-url=https://books.google.com/books?id=p9Mj_KPzJ2YC&pg=PA113 |pages=113–8 |title=Water recreation and disease. Plausibility of associated infections: Acute effects, sequelae and mortality |url=https://www.who.int/water_sanitation_health/bathing/recreadis/en/ |archive-url=https://web.archive.org/web/20130630162549/http://www.who.int/water_sanitation_health/bathing/recreadis/en/ |url-status=dead |archive-date=June 30, 2013 |publisher=WHO |isbn=978-92-4-156305-5}}</ref><ref>{{cite web |title=Shigellosis |url=http://www.eazwv.org/sites/default/files/Files/Infectious%20Diseases%20Handbook/Fact%20Sheets/094%20Shigellosis.pdf |publisher=European Association of Zoo and Wildlife Veterinarians |url-status=dead |archive-url=https://web.archive.org/web/20150927220932/http://www.eazwv.org/sites/default/files/Files/Infectious%20Diseases%20Handbook/Fact%20Sheets/094%20Shigellosis.pdf |archive-date=2015-09-27 }}</ref> During infection, it typically causes [[dysentery]].<ref>{{cite book |editor1-first=Cedric |editor1-last=Mims |editor2-first=Hazel |editor2-last=Dockrell |editor3-first=Richard |editor3-last=Goering |editor4-first=Ivan |editor4-last=Roitt |editor5-first=Derek |editor5-last=Wakelin |editor6-first=Mark |editor6-last=Zuckerman |title=Medical Microbiology |edition=3rd |publisher=Mosby |year=2004 |isbn=978-0-7234-3259-3 |page=287}}</ref>

''Shigella'' is a leading cause of bacterial [[diarrhea]] worldwide, with 80–165 million annual cases (estimated)<ref name=YellowBook/> and 74,000 to 600,000 deaths.<ref name=YellowBook>{{cite book|chapter-url=http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/shigellosis |access-date=22 June 2016 |title=The Yellow Book: Health Information for International Travel |publisher=CDC |isbn=978-0-19-937915-6 |chapter=Chapter 3: Infectious Diseases Related to Travel |author=Bowen A |date=2016}}</ref><ref name=":0">{{Cite journal |last1=Mani |first1=Sachin |last2=Wierzba |first2=Thomas |last3=Walker |first3=Richard I |date=2016 |title=Status of vaccine research and development for Shigella|journal=Vaccine |volume=34 |issue=26 |pages=2887–2894 |doi=10.1016/j.vaccine.2016.02.075|pmid=26979135 |doi-access=free }}</ref> It is one of the top four pathogens that cause moderate-to-severe diarrhea in African and South Asian children.<ref>{{Cite journal |last1=Kotloff|first1=Karen L|last2=Nataro|first2=James P|last3=Blackwelder|first3=William C|s2cid=205969172|display-authors=etal |date=2013 |title=Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60844-2/fulltext|journal=The Lancet |volume=382 |issue=9888 |pages=209–222 |doi=10.1016/S0140-6736(13)60844-2 |pmid=23680352 }}</ref>

== Classification ==
''Shigella'' species are classified by three [[serotype|serogroups]] and one [[serotype]]:
* Serogroup ''A'': ''[[Shigella dysenteriae|S. dysenteriae]]'' (15 serotypes)<ref>{{cite journal |last1=Ansaruzzaman |first1=M |last2=Kibriya |first2=AK |last3=Rahman |first3=A |last4=Neogi |first4=PK |last5=Faruque |first5=AS |last6=Rowe |first6=B |last7=Albert |first7=MJ |title=Detection of provisional serovars of ''Shigella dysenteriae'' and designation as ''S. dysenteriae'' serotypes 14 and 15 |journal=Journal of Clinical Microbiology |volume=33 |issue=5 |pages=1423–5 |year=1995 |pmid=7615772 |pmc=228185 |doi= 10.1128/JCM.33.5.1423-1425.1995}}</ref>
* Serogroup ''B'': ''[[Shigella flexneri|S. flexneri]]'' (9 serotypes)<ref>{{cite journal |last1=Knirel |first1=Y. A. |last2=Sun |first2=Q |last3=Senchenkova |first3=SN |last4=Perepelov |first4=AV |last5=Shashkov |first5=AS |last6=Xu |first6=J |s2cid=7360433 |title=O-Antigen Modifications Providing Antigenic Diversity of Shigella flexneri and Underlying Genetic Mechanisms |journal=Biochemistry (Moscow) |volume=80 |pages=901–914 |year=2015 |issue=7 |doi=10.1134/S0006297915070093 |pmid=26542003 |doi-access=free }}</ref>
* Serogroup ''C'': ''[[Shigella boydii|S. boydii]]'' (19 serotypes)<ref>{{cite journal |last1=Yang |first1=Z |last2=Hu |first2=C |last3=Chen |first3=J |last4=Chen |first4=G |last5=Liu |first5=Z |title=A new serotype of Shigella boydii |language=zh |journal=Wei Sheng Wu Xue Bao |volume=30 |issue=4 |pages=284–95 |year=1990 |pmid=2251827 }}</ref>
* Serogroup ''D'': ''[[Shigella sonnei|S. sonnei]]'' (one serotype){{citation needed|date=May 2021}}

Groups ''A''–''C'' are physiologically similar; ''S. sonnei'' (group ''D'') can be differentiated based on biochemical metabolism assays.<ref name=Baron>{{cite book |last1=Hale |first1=Thomas L. |last2=Keusch |first2=Gerald T. |year=1996 |chapter=Shigella |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8038/ |editor1-last=Baron |editor1-first=Samuel |title=Medical microbiology |publisher=University of Texas Medical Branch |location=Galveston, Texas |pmid=21413292 |isbn=978-0-9631172-1-2 |edition=4th }}</ref> Three ''Shigella'' groups are the major disease-causing species: ''S. flexneri'' is the most frequently isolated species worldwide, and accounts for 60% of cases in the developing world; ''S. sonnei'' causes 77% of cases in the developed world, compared to only 15% of cases in the developing world; and ''S. dysenteriae'' is usually the cause of epidemics of dysentery, particularly in confined populations such as refugee camps.<ref name="WHO shigellosis">{{cite book |title=State of the art of new vaccine research and development |series=Immunization, Vaccines and Biologicals |publisher=World Health Organization |year=2006 |chapter-url=http://apps.who.int/iris/bitstream/10665/69348/1/WHO_IVB_06.01_eng.pdf |archive-url=https://web.archive.org/web/20150927050701/http://apps.who.int/iris/bitstream/10665/69348/1/WHO_IVB_06.01_eng.pdf |archive-date=2015-09-27 |url-status=live |chapter=Shigellosis |pages=10–2 }}</ref>

Each of the ''Shigella'' genomes includes a virulence [[plasmid]] that encodes conserved primary virulence determinants. The ''Shigella'' [[chromosome]]s share most of their genes with those of ''E. coli'' K12 strain MG1655, a well-studied model strain.<ref name=Yang2005>{{cite journal |first1=Fan |last1=Yang |first2=Jian |last2=Yang |first3=Xiaobing |last3=Zhang |first4=Lihong |last4=Chen |first5=Yan |last5=Jiang |first6=Yongliang |last6=Yan |first7=Xudong |last7=Tang |first8=Jing |last8=Wang |first9=Zhaohui |last9=Xiong |first10=Jie |last10=Dong |first11=Ying |last11=Xue |first12=Yafang |last12=Zhu |first13=Xingye |last13=Xu |first14=Lilian |last14=Sun |first15=Shuxia |last15=Chen |first16=Huan |last16=Nie |first17=Junping |last17=Peng |first18=Jianguo |last18=Xu |first19=Yu |last19=Wang |first20=Zhenghong |last20=Yuan |first21=Yumei |last21=Wen |first22=Zhijian |last22=Yao |first23=Yan |last23=Shen |first24=Boqin |last24=Qiang |first25=Yunde |last25=Hou |first26=Jun |last26=Yu |first27=Qi |last27=Jin |title=Genome dynamics and diversity of ''Shigella'' species, the etiologic agents of bacillary dysentery |journal=Nucleic Acids Research |volume=33 |issue=19 |pages=6445–58 |year=2005 |pmid=16275786 |pmc=1278947 |doi=10.1093/nar/gki954 }}</ref>

[[Phylogenetics|Phylogenetic]] studies indicate ''Shigella'' is more appropriately treated as a subgroup of ''[[Escherichia]]''<ref>{{Cite journal |last1=Chaudhuri |first1=Roy R. |last2=Henderson |first2=Ian R. |date=2012-03-01 |title=The evolution of the Escherichia coli phylogeny |url=https://www.sciencedirect.com/science/article/pii/S1567134812000068 |journal=Infection, Genetics and Evolution |language=en |volume=12 |issue=2 |pages=214–226 |doi=10.1016/j.meegid.2012.01.005 |pmid=22266241 |bibcode=2012InfGE..12..214C |issn=1567-1348}}</ref> (see ''[[Escherichia coli#Diversity]]'' for details).

== Pathogenesis ==
''Shigella'' infection is typically by [[Fecal–oral route|ingestion]]. Depending on the host's health, fewer than 100 bacterial cells may cause an infection.<ref>{{cite book |last=Levinson |first=Warren E |title=Review of Medical Microbiology and Immunology |year=2006 |publisher=McGraw-Hill Medical Publishing Division |isbn=978-0-07-146031-6 |edition=9th |page=30}}</ref> ''Shigella'' species generally invade the [[epithelium|epithelial]] lining of the [[Large intestine|colon]], causing severe inflammation and death of the cells lining the colon. This inflammation produces the hallmark diarrhea — even [[dysentery]] — of ''Shigella'' infection.<ref name=Baron/> Toxins produced by some strains contribute to disease during infection. [[Shigella flexneri|''S. flexneri'']] strains produce ShET1 and ShET2, which may contribute to diarrhea.<ref name=Baron/> ''S. dysenteriae'' strains produce <!--the [[enterotoxin]]-->  the hemolytic [[Shiga toxin]], similar to the [[verotoxin]] produced by [[enterohemorrhagic Escherichia coli|enterohemorrhagic ''E. coli'']]. Both Shiga toxin and verotoxin are associated with causing potentially fatal [[hemolytic-uremic syndrome]].<ref name=Baron/>

Because they do not interact with the apical surface of epithelial cells — preferring the basolateral side ''— Shigella'' species invade the host through the [[M-cells]] interspersed in the epithelia of the [[small intestine]].<ref name="Mounier">{{cite journal | title=Shigella flexneri Enters Human Colonic Caco-2 Epithelial Cells through the Basolateral Pole | author=Mounier, Joëlle | journal=Infection and Immunity |date=January 1992 | volume=60 | issue=1 | pages=237–248 | pmc=257528 | first2=T | last3=Hellio | first3=R | last4=Lesourd | first4=M | last5=Sansonetti | first5=PJ | pmid=1729185| last2=Vasselon | doi=10.1128/IAI.60.1.237-248.1992 }}</ref> ''Shigella'' uses a [[Type III secretion system|type-III secretion system]] that acts as a biological syringe to translocate toxic effector proteins to the target human cell. The effector proteins can alter the metabolism of the target cell — leading, for example, to the [[lysis]] of [[Vacuole|vacuolar]] membranes or reorganization of actin polymerization to facilitate intracellular motility of ''Shigella'' bacteria inside the host cell. For instance, the IcsA effector protein (an autotransporter, not a type-III secretion-system effector) triggers actin reorganization by [[Wiskott–Aldrich syndrome protein|N-WASP]] recruitment of [[Arp2/3 complex]]es,  promoting cell-to-cell spread.<ref>{{Cite journal|last1=Snapper|first1=Scott B.|last2=Takeshima|first2=Fuminao|last3=Antón|first3=Inés|last4=Liu|first4=Ching-Hui|last5=Thomas|first5=Sheila M.|last6=Nguyen|first6=Deanna|last7=Dudley|first7=Darryll|last8=Fraser|first8=Hunter|last9=Purich|first9=Daniel|s2cid=23962367|date=October 2001|title=N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility|journal=Nature Cell Biology|language=En|volume=3|issue=10|pages=897–904|doi=10.1038/ncb1001-897|pmid=11584271|issn=1476-4679}}</ref>
The Type III Secretion System (T3SS) plays a crucial role when Shigella secretes its OspC1 and OspC3 proteins to suppress the interferon (IFN) signaling pathway and inhibit the host defense against Shigella. These proteins have been found to target the JAK/STAT signaling pathway, reducing and preventing interferon-stimulated gene (ISG) expression.

OspC1 and OspC3 inhibit IFN signaling by binding to calmodulin (CaM), which is required for the phosphorylation of STAT. These Shigella proteins interact with CaM through their N-terminal α-helix, which mimics the interaction with CaMKII. As a result, CaM mistakenly recognizes the bacterial proteins as CaMKII, preventing the normal function of the signaling pathway and blocking ISG expression.

While bacterial inhibition of the IFN signaling pathway remains largely unexplored, it is a well-studied mechanism in viruses. However, research by Alponde et al. (2022) identified homologous proteins and provided strong evidence that inhibiting IFN signaling is a conserved bacterial strategy.|Alponde, R., Ceccarelli, D. F., Wu, X., Dhe-Paganon, S., & Park, E. (2022).| Bacterial calmodulin inhibitors block host innate immune signaling.| Cell, |185(12),| 2090-2103.|https://doi.org/10.1016/j.cell.2022.04.025</ref>

After infection, ''Shigella'' cells multiply [[Pathogenic bacteria#Intracellular|intracellularly]] and spread to neighboring epithelial cells, resulting in tissue destruction and the characteristic [[pathology]] of shigellosis.<ref>{{cite web |url=http://textbookofbacteriology.net/Shigella_2.html |first=Kenneth |last=Todar |title=''Shigella'' and Shigellosis |work=Todar's Online Textbook of Bacteriology}}{{self-published source|date=September 2015}}</ref>{{self-published inline|date=September 2015}}<ref>{{cite journal |first1=Toshihiko |last1=Suzuki |first2=Chihiro |last2=Sasakawa |title=Molecular basis of the intracellular spreading of ''Shigella'' |journal=Infection and Immunity |volume=69 |issue=10 |pages=5959–66 |year=2001 |pmid=11553531 |pmc=98722 |doi=10.1128/IAI.69.10.5959-5966.2001 }}</ref> The most common symptoms are [[diarrhea]], [[fever]], [[nausea]], [[vomiting]], [[stomach cramp]]s, and [[flatulence]]. Infection is also commonly known to cause large and painful bowel movements. The stool may contain blood, mucus, or pus. Hence, ''Shigella'' cells may cause dysentery. In rare cases, young children may have [[Epileptic seizure|seizures]]. Symptoms can take as long as a week to appear, but most often begin two to four days after ingestion. Symptoms usually last for several days, but can last for weeks. ''Shigella'' is implicated as one of the pathogenic causes of [[reactive arthritis]] worldwide.<ref>{{cite journal |last1=Hill Gaston |first1=J |title=Arthritis associated with enteric infection |journal=Best Practice & Research Clinical Rheumatology |volume=17 |issue=2 |pages=219–39 |year=2003 |pmid=12787523 |doi=10.1016/S1521-6942(02)00104-3 }}</ref>

==Discovery==
The ''Shigella'' genus is named after Japanese physician [[Kiyoshi Shiga]], who researched the cause of dysentery.<ref name="t380">{{cite book | last=Paradise | first=L.J. | last2=Bendinelli | first2=M. | last3=Friedman | first3=H. | title=Enteric Infections and Immunity | publisher=Springer US | series=Infectious Agents and Pathogenesis | year=2013 | isbn=978-1-4899-0313-6 | url=https://books.google.com/books?id=w23lBwAAQBAJ&pg=PA79 | access-date=2025-03-12 | page=79}}</ref> Shiga entered the Tokyo Imperial University School of Medicine in 1892, during which he attended a lecture by [[Kitasato Shibasaburō|Shibasaburo Kitasato]]. Shiga was impressed by Kitasato's intellect and confidence, so after graduating, he went to work for him as a research assistant at the Institute for Infectious Diseases. In 1897, Shiga focused his efforts on what the Japanese referred to as a ''sekiri'' (dysentery) outbreak. Such epidemics were detrimental to the Japanese people and occurred often in the late 19th century. The 1897 ''sekiri'' epidemic affected >91,000, with a mortality rate of >20%.<ref>{{Cite journal|last1=Trofa|first1=Andrew F.|last2=Ueno-Olsen|first2=Hannah|last3=Oiwa|first3=Ruiko|last4=Yoshikawa|first4=Masanosuke|date=1999-11-01|title=Dr. Kiyoshi Shiga: Discoverer of the Dysentery Bacillus|journal=Clinical Infectious Diseases|language=en|volume=29|issue=5|pages=1303–1306|doi=10.1086/313437|pmid=10524979|issn=1058-4838|doi-access=free}}</ref> Shiga studied 32 dysentery patients and used [[Koch's postulates]] to successfully isolate and identify the bacterium causing the disease. He continued to study and characterize the bacterium, identified its methods of (Shiga-) toxin production, and worked to create a vaccine for the disease.{{citation needed|date=March 2023}}

== See also ==
* [[Apocholate citrate agar]]
* [[Enterotoxigenic Escherichia coli|Enterotoxigenic ''E. coli'']]
* [[Enteroinvasive Escherichia coli|Enteroinvasive ''E. coli'']]
* [[Gastroenteritis]]

== References ==
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==External links==
* [https://patricbrc.org/view/Taxonomy/620#view_tab=overview Shigella] genomes and related information at [http://patricbrc.org/ PATRIC], a Bioinformatics Resource Center funded by [https://www.niaid.nih.gov/ NIAID]
* [http://www.path.org/vaccineresources/shigella-etec.php Vaccine Resource Library: Shigellosis and enterotoxigenic ''Escherichia coli'' (ETEC)]
* [https://www.cdc.gov/shigella/ US Centers for Disease Control and Prevention. ''Shigella'' - Shigellosis]

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