A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epidemiologic classification of organisms to a level below the species. [1] [2] [3] [ clarification needed ] A group of serovars with common antigens is called a serogroup or sometimes serocomplex.[ clarification needed ]
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 ]
Serotypes were discovered in hemolytic streptococci by the American microbiologist Rebecca Lancefield in 1933. [4]
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 ("split antigens"), HLA-A23 and HLA-A24. As a result, A9 is now known as a "broad" serotype. [5] For organisms with many possible serotypes, first obtaining a polyvalent match can reduce the number of tests required. [6]
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. [7] Others such as Shigella (and E. coli) and Salmonella are traditionally detected using a slide agglutination test. [6] [8] HLA types are originally determined with the complement fixation test. [9] Newer procedures include the latex fixation test and various other immunoassays.
"Molecular serotyping" refers to methods that replace the antibody-based test with a test based on the nucleic acid sequence – 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. [10] [11]
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. [12]
HLA Locus | # of Serotypes | Broad Antigens | Split Antigens |
---|---|---|---|
A | 25 | 4 | 15 |
B | 50 | 9 | |
C * | 12 | 1 | |
DR | 21 | 4 | |
DQ | 8 | 2 | |
DP * | |||
*DP and many Cw require SSP-PCR for typing. |
Most bacteria produce antigenic substances on the outer surface that can be distinguished by serotyping.
The LPS (O) and capsule (K) antigens are themselves important pathogenicity factors. [6] [15]
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. [16]
E. coli have 187 possible O antigens (6 later removed from list, 3 actually producing no LPS), [17] 53 H antigens, [18] and at least 72 K antigens. [19] 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. [17]
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. [6] Some of these O antigens have equivalents in E. coli, which also cladistically include Shigella. [20]
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. [21] A Salmonella serotype is determined by the unique combination of reactions of cell surface antigens. For Salmonella, the O and H antigens are used. [22] 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 reactions on 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. [8] Additional serotyping methods and alternative subtyping methodologies have been reviewed by Wattiau et al. [23]
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. [24]
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Many other organisms can be classified using recognition by antibodies.
Enterobacteriaceae is a large family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of family is still a subject of debate, but one classification places it in the order Enterobacterales of the class Gammaproteobacteria in the phylum Pseudomonadota. In 2016, the description and members of this family were emended based on comparative genomic analyses by Adeolu et al.
Escherichia coli ( ESH-ə-RIK-ee-ə KOH-lye) is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes such as EPEC, and ETEC are pathogenic and can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains are part of the normal microbiota of the gut and are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of E. coli benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between E. coli and humans are a type of mutualistic biological relationship — where both the humans and the E. coli are benefitting each other. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.
Salmonella is a genus of rod-shaped (bacillus) gram-negative bacteria of the family Enterobacteriaceae. The two known species of Salmonella are Salmonella enterica and Salmonella bongori. S. enterica is the type species and is further divided into six subspecies that include over 2,650 serotypes. Salmonella was named after Daniel Elmer Salmon (1850–1914), an American veterinary surgeon.
Shigella is a genus of bacteria that is Gram-negative, facultatively anaerobic, non–spore-forming, nonmotile, rod-shaped, and is genetically closely related to Escherichia. The genus is named after Kiyoshi Shiga, who discovered it in 1897.
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. Shiga-like toxin (SLT) is a historical term for similar or identical toxins produced by Escherichia coli. The most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli, which include serotypes O157:H7, and O104:H4.
Salmonellosis is a symptomatic infection caused by bacteria of the Salmonella type. It is the most common disease to be known as food poisoning, these are defined as diseases, usually either infectious or toxic in nature, caused by agents that enter the body through the ingestion of food. In humans, the most common symptoms are diarrhea, fever, abdominal cramps, and vomiting. Symptoms typically occur between 12 hours and 36 hours after exposure, and last from two to seven days. Occasionally more significant disease can result in dehydration. The old, young, and others with a weakened immune system are more likely to develop severe disease. Specific types of Salmonella can result in typhoid fever or paratyphoid fever. Typhoid fever and paratyphoid fever are specific types of salmonellosis, known collectively as enteric fever, and are, respectively, caused by salmonella typhi and paratyphi bacteria, which are only found in humans. Most commonly, salmonellosis cases arise from salmonella bacteria from animals, and chicken is a major source for these infections.
The bacterial capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.
Bacillary dysentery is a type of dysentery, and is a severe form of shigellosis. It is associated with species of bacteria from the family Enterobacteriaceae. The term is usually restricted to Shigella infections.
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future. Shigella are closely related to Escherichia coli, but can be differentiated from E.coli based on pathogenicity, physiology and serology.
The quellung reaction, also called the Neufeld reaction, is a biochemical reaction in which antibodies bind to the bacterial capsule of Streptococcus pneumoniae, Klebsiella pneumoniae, Neisseria meningitidis, Bacillus anthracis, Haemophilus influenzae, Escherichia coli, and Salmonella. The antibody reaction allows these species to be visualized under a microscope. If the reaction is positive, the capsule becomes opaque and appears to enlarge.
The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.
Leucine responsive protein, or Lrp, is a global regulator protein, meaning that it regulates the biosynthesis of leucine, as well as the other branched-chain amino acids, valine and isoleucine. In bacteria, it is encoded by the lrp gene.
Hektoen enteric agar is a selective and differential agar primarily used to recover Salmonella and Shigella from patient specimens. HEA contains indicators of lactose fermentation and hydrogen sulfide production; as well as inhibitors to prevent the growth of Gram-positive bacteria. It is named after the Hektoen Institute in Chicago, where researchers developed the agar.
Pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae.
Viable but nonculturable (VBNC) bacteria refers as to bacteria that are in a state of very low metabolic activity and do not divide, but are alive and have the ability to become culturable once resuscitated.
Salmonella enterica subsp. enterica is a subspecies of Salmonella enterica, the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the S. enterica species are in this subspecies, including that responsible for typhoid.
Cytolethal distending toxins are a class of heterotrimeric toxins produced by certain gram-negative bacteria that display DNase activity. These toxins trigger G2/M cell cycle arrest in specific mammalian cell lines, leading to the enlarged or distended cells for which these toxins are named. Affected cells die by apoptosis.
Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.
Edward Thomas Ryan is an American microbiologist, immunologist, and physician at Harvard University and Massachusetts General Hospital. Ryan served as president of the American Society of Tropical Medicine and Hygiene from 2009 to 2010. Ryan is Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, Professor of Medicine at Harvard Medical School, and Director of Global Infectious Diseases at the Massachusetts General Hospital. Ryan's research and clinical focus has been on infectious diseases associated with residing in, immigrating from, or traveling through resource-limited areas. Ryan is a Fellow of the American Society of Microbiology, the American Society of Tropical Medicine and Hygiene, the American College of Physicians, and the Infectious Diseases Society of America.
The mobilized colistin resistance (mcr) gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections. mcr-1, the original variant, is capable of horizontal transfer between different strains of a bacterial species. After discovery in November 2015 in E. coli from a pig in China it has been found in Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. As of 2017, it has been detected in more than 30 countries on 5 continents in less than a year.
However, similar to all molecular assays, genotyping assay does not necessary correlate with phenotypic assay as genes may not be expressed.
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.