View source for Serotype

{{short description|Distinct variation within a species of bacteria or virus or among immune cells}}
{{distinguish|Stereotype}}
[[File:Serotypes – Antibody versus antigen.svg|thumb|right|300px|Two serotypes 1a and 1b with [[antigens]] 2a and 2b on surface, which are recognized by two distinct [[antibodies]], 3a and 3b, respectively]]
A '''serotype''' or '''serovar''' is a distinct variation within a [[species]] of [[bacteria]] or [[virus]] or among [[immune cells]] of different individuals. These [[microorganism]]s, viruses, or [[Cell (biology)|cell]]s are classified together based on their surface [[antigen]]s, allowing the epidemiologic classification of organisms to a [[Infraspecific name|level below the species]].<ref name=Barron>{{cite book | author =  Baron EJ | title = Classification. ''In:'' Baron's Medical Microbiology| editor = Baron S| display-editors = etal| edition = 4th | publisher = Univ of Texas Medical Branch | year = 1996 | id = [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.352 (via NCBI Bookshelf)] | isbn =  978-0-9631172-1-2}}</ref><ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG, Sherris JC | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0}}</ref><ref>{{cite web | title = Serovar | work = The American Heritage Medical Dictionary | date = 2007 | publisher = Houghton Mifflin Company | url = http://medical-dictionary.thefreedictionary.com/serovar }}</ref>{{Clarify|reason=If pathogen A has multiple antigens, and pathogen B has similar antigens but one is different, how does this affect serotype? Is serotype the COMBINATION of antigens? Is it each individual antigen?|date=December 2020}} A group of serovars with common antigens is called a '''serogroup''' or sometimes ''serocomplex''.{{Clarify|reason=This sentence isn't clear. Could use an example here.|date=December 2020}}
Serotyping often plays an essential role in determining species and subspecies. The ''[[Salmonella]]'' [[genus]] of bacteria, for example, has been determined to have over 2600 serotypes. ''[[Vibrio cholerae]]'', the species of bacteria that causes [[cholera]], has over 200 serotypes, based on cell antigens. Only two of them have been observed to produce the potent [[enterotoxin]] that results in cholera: O1 and O139.{{citation needed|date=August 2021}}
Serotypes were discovered in hemolytic [[streptococci]] by the American microbiologist [[Rebecca Lancefield]] in 1933.<ref name=Lancefield_1933>{{cite journal | vauthors = Lancefield RC | title =  A Serological Differentiation of Human and Other Groups of Hemolytic Streptococci | journal = The Journal of Experimental Medicine | volume = 57 | issue = 4 | pages = 571–95 | date = March 1933 | pmid = 19870148 | pmc = 2132252 | doi = 10.1084/jem.57.4.571 }}</ref>
== Procedure ==
''Serotyping'' is the process of determining the ''serotype'' of an organism, using prepared [[antisera]] that bind to a set of known antigens. Some antisera detect multiple known antigens and are known as ''polyvalent'' or ''broad''; others are ''monovalent''. For example, what was once described as [[HLA-A9]] is now subdivided into two more specific serotypes ("[[wikt:split antigen|split antigen]]s"), [[HLA-A23]] and [[HLA-A24]]. As a result, A9 is now known as a "broad" serotype.<ref name="pmid8773320">{{cite journal |vauthors=Fussell H, Thomas M, Street J, Darke C | title = HLA-A9 antibodies and epitopes | journal = Tissue Antigens | volume = 47 | issue = 4 | pages = 307–12 | year = 1996 | pmid = 8773320 | doi =10.1111/j.1399-0039.1996.tb02558.x }}</ref> For organisms with many possible serotypes, first obtaining a polyvalent match can reduce the number of tests required.<ref name=Shig/>
The binding between a surface antigen and the antiserum can be experimentally observed in many forms. A number of bacteria species, including ''[[Streptococcus pneumoniae]]'', display the [[Quellung reaction]] visible under a microscope.<ref>{{cite journal |last1=Habib |first1=M |last2=Porter |first2=BD |last3=Satzke |first3=C |title=Capsular serotyping of Streptococcus pneumoniae using the Quellung reaction. |journal=Journal of Visualized Experiments  |date=24 February 2014 |issue=84 |pages=e51208 |doi=10.3791/51208 |pmid=24637727|pmc=4131683 |doi-access=free }}</ref> Others such as ''Shigella'' (and ''E. coli'') and ''Salmonella'' are traditionally detected using a slide agglutination test.<ref name=Shig>{{cite web |title=Laboratory Protocol: "Serotyping of Shigella spp." |url=https://antimicrobialresistance.dk/CustomerData/Files/Folders/6-pdf-protocols/58_23-10-gfn-shigellaserotypification-final-29-06-10.pdf |website=WHO Global Foodborne Infections Network}}</ref><ref name=SalSlide/> HLA types are originally determined with the [[complement fixation test]].<ref>{{cite book |title=The Serology of HLA-A, -B, and -C |series=Clinical Immunobiology |date=1980 |doi=10.1016/B978-0-12-070004-2.50012-8 |last1=Kissmeyer-Nielsen |first1=F. |volume=4 |pages=99–111 |isbn=9780120700042 }}</ref> Newer procedures include the [[latex fixation test]] and various other [[immunoassay]]s.
"Molecular serotyping" refers to methods that replace the antibody-based test with a test based on the [[nucleic acid]] sequence &ndash; therefore actually a kind of [[genotyping]]. By analyzing which surface antigen-defining allele(s) are present, these methods can produce faster results. However, their results may not always agree with traditional serotyping, as they can fail to account for factors that affect the expression of antigen-determining genes.<ref>{{cite journal | vauthors = Luo Y, Huang C, Ye J, Octavia S, Wang H, Dunbar SA, Jin D, Tang YW, Lan R | display-authors = 6 | title = Comparison of xMAP ''Salmonella'' Serotyping Assay With Traditional Serotyping and Discordance Resolution by Whole Genome Sequencing | journal = Frontiers in Cellular and Infection Microbiology | volume = 10 | page = 452 | date = 2020-09-07 | pmid = 33014887 | pmc = 7504902 | doi = 10.3389/fcimb.2020.00452 | doi-access = free |quote=However, similar to all molecular assays, genotyping assay does not necessary correlate with phenotypic assay as genes may not be expressed.}}</ref><ref name=E_coli_mol>{{cite journal |last1=Lacher |first1=DW |last2=Gangiredla |first2=J |last3=Jackson |first3=SA |last4=Elkins |first4=CA |last5=Feng |first5=PC |title=Novel microarray design for molecular serotyping of shiga toxin- producing Escherichia coli strains isolated from fresh produce. |journal=Applied and Environmental Microbiology |date=August 2014 |volume=80 |issue=15 |pages=4677–4682 |doi=10.1128/AEM.01049-14 |pmid=24837388|pmc=4148803 |bibcode=2014ApEnM..80.4677L |quote=Furthermore, the array identified the H types of 97% of the produce STEC strains compared to 65% by serology, including six strains that were mistyped by serology. |doi-access=free }}</ref>
==Role in organ transplantation==
[[File:Anti-HLA agglutinated RBC.png|frame|right|Agglutination of [[HLA-A3]] positive [[red blood cell]]s with anti-A3 alloreactive [[antisera]] containing Anti-A3 [[IgM]]]]
The [[immune system]] is capable of discerning a cell as being 'self' or 'non-self' according to that cell's serotype. In humans, that serotype is largely determined by [[human leukocyte antigen]] (HLA), the human version of the [[major histocompatibility complex]]. Cells determined to be non-self are usually recognized by the immune system as foreign, causing an immune response, such as [[hemagglutination]]. Serotypes differ widely between individuals; therefore, if cells from one human (or animal) are introduced into another random human, those cells are often determined to be non-self because they do not match the self-serotype. For this reason, transplants between genetically non-identical humans often induce a problematic immune response in the recipient, leading to [[transplant rejection]]. In some situations, this effect can be reduced by serotyping both recipient and potential donors to determine the closest HLA match.<ref name="pmid11158412">{{cite journal | vauthors = Frohn C, Fricke L, Puchta JC, Kirchner H | title = The effect of HLA-C matching on acute renal transplant rejection | journal = Nephrology, Dialysis, Transplantation | volume = 16 | issue = 2 | pages = 355–60 | date = February 2001 | pmid = 11158412 | doi = 10.1093/ndt/16.2.355 | doi-access =  }}</ref>
===Human leukocyte antigens===
{| class="wikitable" align="left"
|+Serotypes according to HLA (MHC) locus
|-
! HLA Locus || # of Serotypes || Broad Antigens|| Split Antigens
|-align = "center"
| '''[[HLA-A|A]]''' || 25 || 4 || 15
|-align = "center"
| '''[[HLA-B|B]]''' || 50 || 9 ||
|-align = "center"
| '''[[HLA-C|C]]'''* || 12 || 1 ||
|-align = "center"
|'''[[HLA-DR|DR]]''' || 21 || 4 ||
|-align = "center"
| '''[[HLA-DQ|DQ]]''' || 8 || 2 ||
|-align = "center"
| '''[[HLA-DP|DP]]'''* || || ||
|-
|colspan = "4" |*DP and many Cw require [[Single Specific Primer-PCR|SSP-PCR]] for typing.
|}{{clear left}}
== Bacteria ==
Most bacteria produce antigenic substances on the outer surface that can be distinguished by serotyping.
* Almost all species of [[Gram-negative bacteria]] produce a layer of [[lipopolysaccharide]] on the outer membrane. The outermost portion of the LPS accessible to antibodies is the ''O antigen''. Variation in the O antigen can be caused by genetic differences in the biosynthetic pathway or the tranporter used to move the building-blocks to the outside of the cell.<ref>{{cite book |last1=Wang |first1=L |last2=Wang |first2=Q |last3=Reeves |first3=PR |chapter=The Variation of O Antigens in Gram-Negative Bacteria |series=Subcellular Biochemistry |title=Endotoxins: Structure, Function and Recognition |date=2010 |volume=53 |pages=123–52 |doi=10.1007/978-90-481-9078-2_6 |pmid=20593265|isbn=978-90-481-9077-5 }}</ref>
* The [[flagella]] on motile bacteria is called the ''H antigen'' in serotyping. Minute genetic differences in the components of the flagella lead to variations detectable by antibodies.<ref name=E_coli_H7>{{cite journal |last1=Ratiner |first1=YA |last2=Salmenlinna |first2=S |last3=Eklund |first3=M |last4=Keskimäki |first4=M |last5=Siitonen |first5=A |title=Serology and genetics of the flagellar antigen of Escherichia coli O157:H7a,7c. |journal=Journal of Clinical Microbiology |date=March 2003 |volume=41 |issue=3 |pages=1033–40 |doi=10.1128/JCM.41.3.1033-1040.2003 |pmid=12624026|pmc=150270 }}</ref>
* Some bacteria produce a [[polysaccharide capsule]], called the ''K antigen'' in serotyping.<ref name="E_coli_K1">{{cite journal |last1=Arredondo-Alonso |first1=Sergio |last2=Blundell-Hunter |first2=George |last3=Fu |first3=Zuyi |last4=Gladstone |first4=Rebecca A. |last5=Fillol-Salom |first5=Alfred |last6=Loraine |first6=Jessica |last7=Cloutman-Green |first7=Elaine |last8=Johnsen |first8=Pål J. |last9=Samuelsen |first9=Ørjan |last10=Pöntinen |first10=Anna K. |last11=Cléon |first11=François |last12=Chavez-Bueno |first12=Susana |last13=De la Cruz |first13=Miguel A. |last14=Ares |first14=Miguel A. |last15=Vongsouvath |first15=Manivanh |last16=Chmielarczyk |first16=Agnieszka |last17=Horner |first17=Carolyne |last18=Klein |first18=Nigel |last19=McNally |first19=Alan |last20=Reis |first20=Joice N. |last21=Penadés |first21=José R. |last22=Thomson |first22=Nicholas R. |last23=Corander |first23=Jukka |last24=Taylor |first24=Peter W. |last25=McCarthy |first25=Alex J. |title=Evolutionary and functional history of the Escherichia coli K1 capsule |journal=Nature Communications |date=15 June 2023 |volume=14 |issue=1 |page=3294 |doi=10.1038/s41467-023-39052-w|pmid=37322051 |pmc=10272209 |bibcode=2023NatCo..14.3294A |doi-access=free }}</ref>
The LPS (O) and capsule (K) antigens are themselves important [[pathogenicity factor]]s.<ref name=Shig/><ref name="E_coli_K1"/>
Some antigens are invariant among a taxonomic group. Presence of these antigens would not be useful for classification lower than the species level, but may inform identification. One example is the [[enterobacterial common antigen]] (ECA), universal to all [[Enterobacterales]].<ref>{{cite journal |last1=Rai |first1=AK |last2=Mitchell |first2=AM |title=Enterobacterial Common Antigen: Synthesis and Function of an Enigmatic Molecule. |journal=mBio |date=11 August 2020 |volume=11 |issue=4 |doi=10.1128/mBio.01914-20 |pmid=32788387|pmc=7439462 |doi-access=free }}</ref>
=== ''E. coli'' ===
''E. coli'' have 187 possible O antigens (6 later removed from list, 3 actually producing no LPS),<ref name="E_coli_O">{{cite journal |last1=Liu |first1=Bin |last2=Furevi |first2=Axel |last3=Perepelov |first3=Andrei V |last4=Guo |first4=Xi |last5=Cao |first5=Hengchun |last6=Wang |first6=Quan |last7=Reeves |first7=Peter R |last8=Knirel |first8=Yuriy A |last9=Wang |first9=Lei |last10=Widmalm |first10=Göran |title=Structure and genetics of Escherichia coli O antigens |journal=FEMS Microbiology Reviews |date=24 November 2020 |volume=44 |issue=6 |pages=655–683 |doi=10.1093/femsre/fuz028|pmid=31778182 |pmc=7685785 |doi-access=free }}</ref> 53 H antigens,<ref name=Wang2003>
{{cite journal|author1=Wang L |author2=Rothemund D |author3=Reeves PR |title=Species-Wide Variation in the ''Escherichia coli'' Flagellin (H-Antigen) Gene |journal=Journal of Bacteriology |date=May 2003 |volume=185 |issue=9 |pages=2396–2943 |pmc=154406 |doi=10.1128/JB.185.9.2936-2943.2003 |pmid=12700273}}</ref> and at least 72 K antigens.<ref name="E_coli_K">{{cite journal |last1=Kunduru |first1=BR |last2=Nair |first2=SA |last3=Rathinavelan |first3=T |title=EK3D: an E. coli K antigen 3-dimensional structure database. |journal=Nucleic Acids Research |date=4 January 2016 |volume=44 |issue=D1 |pages=D675-81 |doi=10.1093/nar/gkv1313 |pmid=26615200|pmc=4702918 |doi-access=free }}</ref> Among these three, the O antigen has the best correlation with lineages; as a result, the O antigen is used to define the "serogroup" and is also used to define strains in taxonomy and epidemiology.<ref name="E_coli_O"/>
===''Shigella''===
''Shigella'' are only classified by their O antigen, as they are non-motile and produce no flagella. Across the four "species", there are 15 + 11 + 20 + 2 = 48 serotypes.<ref name=Shig/> Some of these O antigens have equivalents in ''E. coli'', which also cladistically include ''Shigella''.<ref>{{cite journal |last1=Liu |first1=Bin |last2=Knirel |first2=Yuriy A. |last3=Feng |first3=Lu |last4=Perepelov |first4=Andrei V. |last5=Senchenkova |first5=Sof'ya N. |last6=Wang |first6=Quan |last7=Reeves |first7=Peter R. |last8=Wang |first8=Lei |title=Structure and genetics of Shigella O antigens |journal=FEMS Microbiology Reviews |date=July 2008 |volume=32 |issue=4 |pages=627–653 |doi=10.1111/j.1574-6976.2008.00114.x|pmid=18422615 |doi-access=free }}</ref>
=== ''Salmonella'' ===
The [[Kauffman–White classification]] scheme is the basis for naming the manifold serovars of ''Salmonella''. To date, more than 2600 different serotypes have been identified.<ref>{{cite journal | vauthors = Gal-Mor O, Boyle EC, Grassl GA | title = Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ | journal = Frontiers in Microbiology | volume = 5 | pages = 391 | pmid = 25136336 | pmc = 4120697 | doi = 10.3389/fmicb.2014.00391 | year = 2014 | doi-access = free }}</ref> A ''Salmonella'' serotype is determined by the unique combination of reactions of cell surface [[antigens]]. For ''Salmonella'', the O and H antigens are used.<ref>{{cite web|title=Serotypes and the Importance of Serotyping Salmonella|url=https://www.cdc.gov/salmonella/reportspubs/salmonella-atlas/serotyping-importance.html|website=CDC|access-date=16 October 2014}}</ref>
There are two species of ''Salmonella'': ''[[Salmonella bongori]]'' and ''[[Salmonella enterica]]''. ''Salmonella enterica'' can be subdivided into six subspecies.
The process to identify the serovar of the bacterium consists of finding the formula of surface antigens which represent the variations of the bacteria.  The traditional method for determining the antigen formula is [[agglutination (biology)|agglutination]] reactions on [[Microscope slide|slides]]. The agglutination between the antigen and the [[antibody]] is made with a specific [[antisera]], which reacts with the antigen to produce a mass. The antigen O is tested with a bacterial suspension from an [[agar plate]], whereas the antigen H is tested with a bacterial suspension from a broth culture. The scheme classifies the serovar depending on its antigen formula obtained via the agglutination reactions.<ref name=SalSlide>{{cite journal| vauthors = Danan C, Fremy S, Moury F, Bohnert ML, Brisabois A | title = Determining the serotype of isolated Salmonella strains in the veterinary sector using the rapid slide agglutination test. | journal = J. Reference | date = 2009 | volume = 2 | pages = 13–8 }}</ref> Additional serotyping methods and alternative subtyping methodologies have been reviewed by Wattiau et al.<ref>{{cite journal | vauthors = Wattiau P, Boland C, Bertrand S | title = Methodologies for Salmonella enterica subsp. enterica subtyping: gold standards and alternatives | journal = Applied and Environmental Microbiology | volume = 77 | issue = 22 | pages = 7877–85 | date = November 2011 | pmid = 21856826 | pmc = 3209009 | doi = 10.1128/AEM.05527-11 | bibcode = 2011ApEnM..77.7877W }}</ref>
===''Streptococcus''===
''Streptococcus pneumoniae'' has 93 capsular serotypes. 91 of these serotypes use the ''Wzy'' enzyme pathway. The ''Wzy'' pathway is used by almost all gram-positive bacteria, by lactococci and streptococci (exopolysacchide), and is also responsible for group 1 and 4 Gram-negative capsules.<ref>{{cite journal |last1=Yother |first1=J |title=Capsules of Streptococcus pneumoniae and other bacteria: paradigms for polysaccharide biosynthesis and regulation. |journal=Annual Review of Microbiology |date=2011 |volume=65 |pages=563–81 |doi=10.1146/annurev.micro.62.081307.162944 |pmid=21721938}}</ref>
== Viruses ==
{{empty section|date=November 2023}}<!-- Useful sources: 15184425 (Dengue, also covers a bunch of methods (well, you can't exactly look for clumping with things this small...)), https://www.woah.org/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/2.03.04_AI.pdf (bird flu A) -->
== Other organisms ==
Many other organisms can be classified using recognition by antibodies.
* The [[malaria]] pathogen ''[[Plasmodium falciparum]]'' is notorious for its many surface antigen variants.<ref>{{cite journal |last1=Chulay |first1=JD |last2=Haynes |first2=JD |last3=Diggs |first3=CL |title=Serotypes of Plasmodium falciparum defined by immune serum inhibition of in vitro growth. |journal=Bulletin of the World Health Organization |date=1985 |volume=63 |issue=2 |pages=317–23 |pmid=3893775|pmc=2536403 }}</ref> A certain vaccine candidate is designed to cover all of these ''serotypes''.<ref>{{cite journal |last1=Cowan |first1=Graeme J. M. |last2=Creasey |first2=Alison M. |last3=Dhanasarnsombut |first3=Kelwalin |last4=Thomas |first4=Alan W. |last5=Remarque |first5=Edmond J. |last6=Cavanagh |first6=David R. |title=A Malaria Vaccine Based on the Polymorphic Block 2 Region of MSP-1 that Elicits a Broad Serotype-Spanning Immune Response |journal=PLOS ONE |date=26 October 2011 |volume=6 |issue=10 |pages=e26616 |doi=10.1371/journal.pone.0026616|pmid=22073118 |pmc=3202563 |bibcode=2011PLoSO...626616C |doi-access=free }}</ref>
* ''[[Toxoplasma gondii]]'' can be classified into serotypes.<ref>{{cite journal |last1=Shobab |first1=Leila |last2=Pleyer |first2=Uwe |last3=Johnsen |first3=Joerdis |last4=Metzner |first4=Sylvia |last5=James |first5=Erick R. |last6=Torun |first6=N. |last7=Fay |first7=Michael P. |last8=Liesenfeld |first8=Oliver |last9=Grigg |first9=Michael E. |title=Toxoplasma Serotype Is Associated With Development of Ocular Toxoplasmosis |journal=The Journal of Infectious Diseases |date=1 November 2013 |volume=208 |issue=9 |pages=1520–1528 |doi=10.1093/infdis/jit313|pmid=23878321 |pmc=3789564 |doi-access=free }}</ref>
* ''[[Trypanosoma cruzi]]'', which causes [[Chagas disease]], can be serotyped using whole parasites.<ref>{{cite journal |last1=Balouz |first1=Virginia |last2=Bracco |first2=Leonel |last3=Ricci |first3=Alejandro D. |last4=Romer |first4=Guadalupe |last5=Agüero |first5=Fernán |last6=Buscaglia |first6=Carlos A. |title=Serological Approaches for Trypanosoma cruzi Strain Typing |journal=Trends in Parasitology |date=March 2021 |volume=37 |issue=3 |pages=214–225 |doi=10.1016/j.pt.2020.12.002|pmid=33436314 |pmc=8900812 }}</ref>
== See also ==
* [[Biovar]]
* [[Morphovar]]
== References ==
{{reflist}}
== External links ==
* [http://www.allelefrequencies.net HLA Allele and Haplotype Frequency Database]
[[Category:Serology]]
[[Category:Speciation]]
[[Category:Biological classification]]
[[Category:Microbiology]]
[[Category:Infraspecific bacteria taxa]]
[[Category:Infraspecific virus taxa]]