Streptococcus pyogenes is a species of Gram-positive bacterium in the genus Streptococcus. These bacteria are aerotolerant and an extracellular bacterium, made up of non-motile and non-sporing cocci, it is clinically important for humans. It is an infrequent, but pathogenic, part of the skin microbiota, it is the predominant species harboring the Lancefield group A antigen, is called group A streptococcus. However, both Streptococcus dysgalactiae and the Streptococcus anginosus group can possess group A antigen. Group A streptococci when grown on blood agar produces small zones of beta-hemolysis, a complete destruction of red blood cells, it is thus called group A streptococcus, can make colonies greater than 5 mm in size. Like other cocci, streptococci are round bacteria; the species name is derived from Greek words meaning'a chain' of berries and pus -forming, because streptococcal cells tend to link in chains of round cells and a number of infections caused by the bacterium, produce pus. The main criterion for differentiation between Staphylococcus spp. and Streptococcus spp. is the catalase test.
Staphylococci are catalase positive. S. pyogenes can be cultured on fresh blood agar plates. Under ideal conditions, it has an incubation period of 1 to 3 days. An estimated 700 million GAS. While the overall mortality rate for these infections is 0.1%, over 650,000 of the cases are severe and invasive, have a mortality rate of 25%. Early recognition and treatment are critical. S. pyogenes colonises the throat, genital mucosa and skin. Of healthy individuals, 1 % to 5 % have vaginal, or rectal carriage. In healthy children, such carriage rate varies from 2% to 17%. There are four methods for the transmission of this bacterium: inhalation of respiratory droplets, skin contact, contact with objects, surface, or dust, contaminated with bacteria or, less transmission through food; such bacteria can cause a variety of diseases such as streptococcal pharyngitis, rheumatic fever, rheumatic heart disease, scarlet fever. Although pharyngitis is viral in origin, about 15 to 30% of all pharyngitis cases in children are caused by GAS.
The number of pharyngitis cases is higher in children when compared with adults due to exposures in schools, as a consequence of lower host immunity. Such cases Streptococcal pharyngitis occurs more from December to April in seasonal countries due to changing climate, behavioural changes or predisposing viral infection. Disease cases are the lowest during autumn. MT1 clone is associated with invasive Streptococcus pyogenes infections among developed countries; the incidence and mortality of S. pyognes was high during the pre-penicillin era, but had started to fall prior to the widespread availability of penicillin. Therefore, environmental factors do play a role in the S. pyogenes infection. Incidence of S. pyogenes is 2 to 4 per 100,000 population in developed countries and 12 to 83 per 100,000 population in developing countries. S. pyogenes infection is more found in men than women, with highest rates in the elderly, followed by infants. In people with risk factors such as heart disease, malignancy, blunt trauma, surgical incision, virus respiratory infection, including influenza, S. pyogenes infection happens in 17 to 25% of all cases.
GAS secondary infection happens within one week of the diagnosis of influenza infection. In 14 to 16% of childhood S. pyogenes infections, there is a prior chickenpox infection. Such S. pyogenes infection in children manifests as severe soft tissue infection with onset 4 to 12 days from the chickenpox diagnosis. There is 40 to 60 times increase in risk of S. pyogenes infection within the first two weeks of chickenpox infection in children. However, 20 to 30% of S. pyogenes infection does occur in adults with no identifiable risk factors. The incidence is higher in children with no known risk factors; the rates of scarlet fever in UK was 4 in 100,000 population, however, in 2014, the rates had risen to 49 per 100,000 population. Rheumatic fever and rheumatic heart disease occurs at 2 to 3 weeks after the throat infection, more common among the impoverished people in developing countries. From 1967 to 1996, the global mean incidence of rheumatic fever and RHD was 19 per 100,000 with the highest incidence at 51 per 100,000.
Maternal S. pyogenes infection happens in late pregnancy. This represents 20 to 100 times increase in risk for S. pyogenes infections. Clinical manifestations are: pneumonia, septic arthritis, necrotizing fasciitis, genital tract sepsis. According to a study done by Queen Charlotte’s hospital in London during the 1930s, the vagina was not the common source of such infection. On the contrary, maternal throat infection and close contacts with carriers were the more common sites for maternal S. pyogenes infection. In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its cell-wall polysaccharide, a virulence factor displayed on its surface. In 1946, Lancefield described the serologic classification of S. pyogenes isolates based on their surface T-antigen. Four of the 20 T-antigens have been revealed to be pili, which are used
Escherichia coli known as E. coli, is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia, found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in their hosts, are responsible for product recalls due to food contamination. The harmless strains are part of the normal microbiota of the gut, can benefit their hosts by producing vitamin K2, preventing colonization of the intestine with pathogenic bacteria, having a symbiotic relationship. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for 3 days, but its numbers decline afterwards. E. Coli and other facultative anaerobes constitute about 0.1% of gut microbiota, fecal–oral transmission is the major route through which pathogenic strains of the bacterium cause disease. Cells are able to survive outside the body for a limited amount of time, which makes them potential indicator organisms to test environmental samples for fecal contamination.
A growing body of research, has examined environmentally persistent E. coli which can survive for extended periods outside a host. The bacterium can be grown and cultured and inexpensively in a laboratory setting, has been intensively investigated for over 60 years. E. coli is a chemoheterotroph whose chemically defined medium must include a source of carbon and energy. E. coli is the most studied prokaryotic model organism, an important species in the fields of biotechnology and microbiology, where it has served as the host organism for the majority of work with recombinant DNA. Under favorable conditions, it takes up to 20 minutes to reproduce. E. coli is a facultative anaerobic and nonsporulating bacterium. Cells are rod-shaped, are about 2.0 μm long and 0.25–1.0 μm in diameter, with a cell volume of 0.6–0.7 μm3. E. Coli stains Gram-negative because its cell wall is composed of a thin peptidoglycan layer and an outer membrane. During the staining process, E. coli picks up the color of the counterstain safranin and stains pink.
The outer membrane surrounding the cell wall provides a barrier to certain antibiotics such that E. coli is not damaged by penicillin. Strains that possess flagella are motile; the flagella have a peritrichous arrangement. It attaches and effaces to the microvilli of the intestines via an adhesion molecule known as intimin. E. coli can live on a wide variety of substrates and uses mixed-acid fermentation in anaerobic conditions, producing lactate, ethanol and carbon dioxide. Since many pathways in mixed-acid fermentation produce hydrogen gas, these pathways require the levels of hydrogen to be low, as is the case when E. coli lives together with hydrogen-consuming organisms, such as methanogens or sulphate-reducing bacteria. Optimum growth of E. coli occurs at 37 °C, but some laboratory strains can multiply at temperatures up to 49 °C. E. coli grows in a variety of defined laboratory media, such as lysogeny broth, or any medium that contains glucose, ammonium phosphate monobasic, sodium chloride, magnesium sulfate, potassium phosphate dibasic, water.
Growth can be driven by aerobic or anaerobic respiration, using a large variety of redox pairs, including the oxidation of pyruvic acid, formic acid and amino acids, the reduction of substrates such as oxygen, fumarate, dimethyl sulfoxide, trimethylamine N-oxide. E. coli is classified as a facultative anaerobe. It uses oxygen when it is available, it can, continue to grow in the absence of oxygen using fermentation or anaerobic respiration. The ability to continue growing in the absence of oxygen is an advantage to bacteria because their survival is increased in environments where water predominates; the bacterial cell cycle is divided into three stages. The B period occurs between the beginning of DNA replication; the C period encompasses the time it takes to replicate the chromosomal DNA. The D period refers to the stage between the conclusion of DNA replication and the end of cell division; the doubling rate of E. coli is higher. However, the length of the C and D periods do not change when the doubling time becomes less than the sum of the C and D periods.
At the fastest growth rates, replication begins before the previous round of replication has completed, resulting in multiple replication forks along the DNA and overlapping cell cycles. E. coli and related bacteria possess the ability to transfer DNA via bacterial conjugation or transduction, which allows genetic material to spread horizontally through an existing population. The process of transduction, which uses the bacterial virus called a bacteriophage, is where the spread of the gene encoding for the Shiga toxin from the Shigella bacteria to E. coli helped produce E. coli O157:H7, the Shiga toxin-producing strain of E. coli. E. coli encompasses an enormous population of bacteria that exhibit a high degree of both genetic and phenotypic diversity. Genome sequencing of a large number of isolates of E. coli and related bacteria shows that a taxonomic reclassification would be desirable. However, this has not been done due to its medical importance, E. coli remains one of the most diverse bacterial species: only 20% of the genes in a typical E. coli genome is shared among all strains.
In fact, from the evolutionary point of view, the members of genus Shigella (S. dysenteriae, S. fle
Heat-stable enterotoxins are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli which are in general toxic to animals. These peptides keep their 3D structure and remain active at temperatures as high as 100 °C. Different STs recognize distinct receptors on the surface of animal cells and thereby affect different intracellular signaling pathways. For example, STa enterotoxins bind and activate membrane-bound guanylate cyclase, which leads to the intracellular accumulation of cyclic GMP and downstream effects on several signaling pathways; these events lead to the loss of electrolytes and water from intestinal cells. Heat-stable toxin 1 of entero-aggregative Escherichia coli is a small toxin, it is not, however associated with entero-aggregative E. coli but with many other diarrhoeic E. coli families. Some studies have established the role of EAST1 in some human outbreaks of diarrhoea. Isolates from farm animals have been shown to carry the astA gene coding for EAST1.
However, the relation between the presence of EAST1 and disease is not conclusive. The mature STa protein from Escherichia coli, the cause of acute diarrhoea in infants and travellers in developing countries, is a 19-residue peptide containing three disulphide bridges that are functionally important. STa contains an N-terminal signal peptide composed of two domains and Pro, involved in extracellular toxin release, a core enterotoxigenic domain. Members of heat-stable enterotoxin B family assume a helical secondary structure, with two alpha helices forming a disulfide cross-linked alpha-helical hairpin; the disulfide bonds are crucial for the toxic activity of the protein, are required for maintenance of the tertiary structure, subsequent interaction with the particulate form of guanylate cyclase, increasing cyclic GMP levels within the host intestinal epithelial cells
A T cell, or T lymphocyte, is a type of lymphocyte that plays a central role in cell-mediated immunity. T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells, by the presence of a T-cell receptor on the cell surface, they are called T cells. The several subsets of T cells each have a distinct function; the majority of human T cells, termed alpha beta T cells, rearrange their alpha and beta chains on the cell receptor and are part of the adaptive immune system. Specialized gamma delta T cells, have invariant T-cell receptors with limited diversity, that can present antigens to other T cells and are considered to be part of the innate immune system. Effector cells are the superset of all the various T cell types that respond to a stimulus, such as co-stimulation; this includes helper, killer and other T cell types. Memory cells are their opposite counterpart that are longer lived to target future infections as necessary. T helper cells assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, activation of cytotoxic T cells and macrophages.
These cells are known as CD4+ T cells because they express the CD4 glycoprotein on their surfaces. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells. Once activated, they divide and secrete small proteins called cytokines that regulate or assist in the active immune response; these cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, TH9, or TFH, which secrete different cytokines to facilitate different types of immune responses. Signalling from the APC directs T cells into particular subtypes. Cytotoxic T cells destroy virus-infected cells and tumor cells, are implicated in transplant rejection; these cells are known as CD8+ T cells since they express the CD8 glycoprotein at their surfaces. These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells. Through IL-10, other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases.
Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell. Appropriate co-stimulation must be present at the time of antigen encounter for this process to occur. Memory T cells were thought to belong to either the effector or central memory subtypes, each with their own distinguishing set of cell surface markers. Subsequently, numerous new populations of memory T cells were discovered including tissue-resident memory T cells, stem memory TSCM cells, virtual memory T cells; the single unifying theme for all memory T cell subtypes is that they are long-lived and can expand to large numbers of effector T cells upon re-exposure to their cognate antigen. By this mechanism they provide the immune system with "memory" against encountered pathogens. Memory T cells may be either CD4+ or CD8+ and express CD45RO. Memory T cell subtypes: Central memory T cells express CD45RO, C-C chemokine receptor type 7, L-selectin.
Central memory T cells have intermediate to high expression of CD44. This memory subpopulation is found in the lymph nodes and in the peripheral circulation.. Effector memory T cells lack expression of CCR7 and L-selectin, they have intermediate to high expression of CD44. These memory T cells lack lymph node-homing receptors and are thus found in the peripheral circulation and tissues. TEMRA stands for terminally differentiated effector memory cells re-expressing CD45RA, a marker found on naive T cells. Tissue resident memory T cells occupy tissues without recirculating. One cell surface marker, associated with TRM is the integrin αeβ7. Virtual memory T cells differ from the other memory subsets in that they do not originate following a strong clonal expansion event. Thus, although this population as a whole is abundant within the peripheral circulation, individual virtual memory T cell clones reside at low frequencies. One theory is. Although CD8 virtual memory T cells were the first to be described, it is now known that CD4 virtual memory cells exist.
Regulatory T cells are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress autoreactive T cells that escaped the process of negative selection in the thymus. Suppressor T cells along with Helper T cells can collectively be called Regulatory T cells due to their regulatory functions. Two major classes of CD4 + Treg cells have been described -- FOXP3 − Treg cells. Regulatory T cells can develop either during normal development in the thymus, are known as thymic Treg cells, or can be induced peripherally and are called peripherally derived Treg cel
Clostridium botulinum is a Gram-positive, rod-shaped, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause a severe flaccid paralytic disease in humans and other animals and is the most potent toxin known to mankind, natural or synthetic, with a lethal dose of 1.3–2.1 ng/kg in humans. C. Botulinum is a diverse group of pathogenic bacteria grouped together by their ability to produce botulinum toxin and now known as four distinct groups, C. botulinum groups I-IV. C. botulinum groups I-IV, as well as some strains of Clostridium butyricum and Clostridium baratii, are the bacteria responsible for producing botulinum toxin. C. Botulinum is responsible for foodborne botulism, infant botulism, wound botulism. C. botulinum produces heat-resistant endospores that are found in soil and are able to survive under adverse conditions. C. Botulinum is associated with bulging canned food. C. botulinum is a rod-shaped, spore-forming bacterium. It is an obligate anaerobe.
However, C. botulinum tolerates traces of oxygen due to the enzyme superoxide dismutase, an important antioxidant defense in nearly all cells exposed to oxygen. C. botulinum is only able to produce the neurotoxin during sporulation, which can only happen in an anaerobic environment. Other bacterial species produce spores in an unfavorable growth environment to preserve the organism's viability and permit survival in a dormant state until the spores are exposed to favorable conditions. C. botulinum is divided into four distinct phenotypic groups and is classified into seven serotypes based on the antigenicity of the botulinum toxin produced. The classification into groups is based on the ability of the organism to digest complex proteins. Studies at the DNA and rRNA level support the subdivision of the species into groups I-IV. Most outbreaks of human botulism are caused by II C. botulinum. Group III organisms cause diseases in animals. Group IV C. botulinum has not been shown to cause animal disease.
Neurotoxin production is the unifying feature of the species. Eight types of toxins have been identified that are allocated a letter, several of which can cause disease in humans, they are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxin to be absorbed from the intestines into the bloodstream. However, all types of botulinum toxin are destroyed by heating to 100 °C for 15 minutes. Most strains produce one type of neurotoxin, but strains producing multiple toxins have been described. C. botulinum producing B and F toxin types have been isolated from human botulism cases in New Mexico and California. The toxin type has been designated Bf as the type B toxin was found in excess to the type F. Similarly, strains producing Ab and Af toxins have been reported. Evidence indicates the neurotoxin genes have been the subject of horizontal gene transfer from a viral source; this theory is supported by the presence of integration sites flanking the toxin in some strains of C. botulinum.
However, these integrations sites are degraded, indicating that the C. botulinum acquired the toxin genes quite far in the evolutionary past. Only botulinum toxin types A, B, E, F and H cause disease in humans. Types A, B, E are associated with food-borne illness, with type E associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals. No disease is associated with type G; the "gold standard" for determining toxin type is a mouse bioassay, but the genes for types A, B, E, F can now be differentiated using quantitative PCR. As no antitoxin to type H is yet available, discovered in 2013 and by far the deadliest, details are kept under shroud. A few strains from organisms genetically identified as other Clostridium species have caused human botulism: C. butyricum has produced type E toxin and C. baratii had produced type F toxin. The ability of C. botulinum to transfer neurotoxin genes to other clostridia is concerning in the food industry, where preservation systems are designed to destroy or inhibit only C. botulinum but not other Clostridium species.
In the laboratory, C. botulinum is isolated in tryptose sulfite cycloserine growth medium in an anaerobic environment with less than 2% oxygen. This can be achieved by several commercial kits that use a chemical reaction to replace O2 with CO2. C. botulinum is a lipase-positive microorganism that grows between pH of 4.8 and 7.0 and cannot use lactose as a primary carbon source, characteristics important for biochemical identification. C. botulinum was first recognized and isolated in 1895 by Emile van Ermengem from home-cured ham implicated in a botulism outbreak. The isolate was named Bacillus botulinus, after the Latin word for sausage, botulus. However, isolates from subsequent outbreaks were always found to be anaerobic spore formers, so Ida A. Bengtson proposed that the organism be placed into the genus Clostridium, as the genus Bacillus was restricted to aerobic spore-forming rods. Since 1959, all species producing the botulinum neurotoxins have been designated C. botulinum. Substantial phenotypic and genotypic evidence exists to demonstrate heterogeneity within the species.
This has led to the
The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes, responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex molecules. The binding between TCR and antigen peptides is of low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR; the TCR is composed of two different protein chains. In humans, in 95% of T cells the TCR consists of an alpha chain and a beta chain, whereas in 5% of T cells the TCR consists of gamma and delta chains; this ratio changes in diseased states. It differs between species. Orthologues of the 4 loci have been mapped in various species; each locus can produce a variety of polypeptides with variable regions. When the TCR engages with antigenic peptide and MHC, the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, activated or released transcription factors.
In 1984, Tak Wah Mak and Mark M. Davis discovered the mouse TCR respectively; these findings allowed the entity and structure of the elusive TCR, known before as the "Holy Grail of Immunology", to be revealed. This allowed scientists from around the world to carry out studies on the TCR, leading to important studies in the fields of CAR-T, Cancer immunotherapy and Checkpoint inhibition; the TCR is a disulfide-linked membrane-anchored heterodimeric protein consisting of the variable alpha and beta chains expressed as part of a complex with the invariant CD3 chain molecules. T cells expressing this receptor are referred to as α:β T cells, though a minority of T cells express an alternate receptor, formed by variable gamma and delta chains, referred as γδ T cells; each chain is composed of two extracellular domains: Variable region and a Constant region, both of Immunoglobulin superfamily domain forming antiparallel β-sheets. The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex.
The variable domain of both the TCR α-chain and β-chain each have three hypervariable or complementarity determining regions. There is an additional area of hypervariability on the β-chain that does not contact antigen and, therefore, is not considered a CDR; the residues in these variable domains are located in two regions of the TCR, at the interface of the α- and β-chains and in the β-chain framework region, thought to be in proximity to the CD3 signal-transduction complex. CDR3 is the main CDR responsible for recognizing processed antigen, although CDR1 of the alpha chain has been shown to interact with the N-terminal part of the antigenic peptide, whereas CDR1 of the β-chain interacts with the C-terminal part of the peptide. CDR2 is thought to recognize the MHC. CDR4 of the β-chain is not thought to participate in antigen recognition, but has been shown to interact with superantigens; the constant domain of the TCR consists of short connecting sequences in which a cysteine residue forms disulfide bonds, which form a link between the two chains.
The TCR is a member of the immunoglobulin superfamily, a large group of proteins involved in binding and adhesion. The TCR is similar to a half-antibody consisting of a single heavy and single light chain, except the heavy chain is without its crystallisable fraction; the two subunits of TCR are twisted together. Whereas the antibody uses its Fc region to bind to Fc Receptors on leukocytes, TCR is docked onto the cell membrane. However, it is not able to mediate signal transduction itself due to its short cytoplasmic tail, so TCR still requires CD3 and zeta to carry out the signal transduction in its place, just as antibodies require binding to FcRs to initiate signal transduction. In this way the MHC-TCR-CD3 interaction for T cells is functionally similar to the antigen-immunoglobulin-FcR interaction for myeloid leukocytes, Ag-Ig-CD79 interaction for B cells; the generation of TCR diversity is similar to that for B cell antigen receptors. It arises from genetic recombination of the DNA encoded segments in individual somatic T cells by somatic VJ recombination using RAG1 and RAG2 recombinases.
Unlike immunoglobulins, however, TCR genes do not undergo somatic hypermutation, T cells do not express activation-induced cytidine deaminase. The recombination pro cess that creates diversity in BCR and TCR is unique to lymphocytes during the early stages of their development in primary lymphoid organs; each recombined TCR possess unique antigen specificity, determined by the structure of the antigen-binding site formed by the α and β chains in case of αβ T cells or γ and δ chains on case of γδ T cells. The TCR alpha chain is generated by VJ recombination, whereas the beta chain is generated by VDJ recombination. Generation of the TCR gamma chain involves VJ recombination, whereas generation of the TCR delta chain occurs by VDJ recombination; the intersection of these specific regions corresponds to the CDR3 region, important for peptide/MHC recognition. It is the un
The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera and hemolytic-uremic syndrome. One component is known as the A subunit, the remaining five components are B subunits. All of these toxins share a similar 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 able to use its catalytic machinery to take over the host cell's regular functions. There are four main families of the AB5 toxin; these families are characterized by the sequence of their A subunit, as well as their catalytic ability. This family is known as Ct or Ctx, includes the heat-labile enterotoxin, known as LT. Cholera toxin’s discovery is credited by many to Dr. Sambhu Nath De, he conducted his research in Calcutta making his discovery in 1959, although it was first purified by Robert Koch in 1883. Cholera toxin is composed of a protein complex, secreted by the bacterium Vibrio cholerae.
Some symptoms of this toxin include chronic and widespread watery diarrhea and dehydration that, in some cases, leads to death. This family is known as Ptx and contains the toxin responsible for whooping cough. Pertussis toxin is secreted by the gram-negative bacterium, Bordetella pertussis. Whooping cough is contagious and cases are increasing in the United States despite vaccination. Symptoms include paroxysmal cough with whooping and vomiting; the bacterium Bordetella pertussis was first identified as the cause of whooping cough and isolated by Jules Bordet and Octave Gengou in France in 1900. The toxin shares its mechanism with cholera toxin. ArtAB toxin of Salmonella enterica has components similar to those found in two different families: the ArtA subunit is homologous with pertussis toxin A, while the ArtB subunit is homologous with subB as well as proteins found in other Salmonella strains. Under the categorize-by-A rule, it is a Ptx-family toxin. Shiga toxin known as Stx, is a toxin, produced by the rod shaped Shigella dysenteriae and Escherichia coli.
Food and drinks contaminated with these bacteria are the source of infection and how this toxin is spread. Symptoms include abdominal pain as well as watery diarrhea. Severe life-threatening cases are characterized by hemorrhagic colitis; the discovery of shiga toxin is credited to Dr. Kiyoshi Shiga in 1898; this family is known as SubAB and was discovered during the 1990s. It produced by strains of STEC that do not have the locus of enterocyte effacement, is known to cause hemolytic-uremic syndrome, it is called a subtilase cytotoxin because its A subunit sequence is similar to that of a subtilase-like serine protease in Bacillus anthracis. Some symptoms caused by this toxin are a decrease in platelet count in the blood or thrombocytopenia, an increase in white blood cell count or leukocytosis, renal cell damage; the subtilase cytotoxin A subunit is a protease known to cleave binding immunoglobulin protein, leading to endoplasmic reticulum stress and cell death. The B subunits bind to N-Glycolylneuraminic acid glycans on cells with high affinity.
Just subB is sufficient to cause vacuolation of vero cells. Neu5GC is not made by humans but is acquired from food sources such as red meat and dairy products frequent sources of STEC infections, into the human gut lining. A complete AB5 toxin complex contains six protein units. Five units are similar or identical in structure and they comprise the B subunit; the last protein unit is known as the A subunit. The A subunit of an AB5 toxin is the portion responsible for catalysis of specific targets. For Shiga toxin family, the A subunit hosts a Trypsin-sensitive region which gives out two fragmented domains when cleaved; this region has not been confirmed for the other AB5 toxin families as yet. In general, the two domains of the A subunit, named A1 and A2, are linked by a disulfide bond. Domain A1 is the part of the toxin responsible for its toxic effects. Domain A2 provides a non-covalent linkage to the B subunit through the B subunit's central pore; the A1 chain for cholera toxin catalyzes the transfer of ADP-ribose from Nicotinamide adenine dinucleotide to arginine or other guanidine compounds by utilizing ADP-ribosylation factors.
In the absence of arginine or simple guanidino compounds, the toxin mediated NAD+ nucleosidase activity proceeds using water as a nucleophile. The B subunits form a five-membered or pentameric ring, where one end of the A subunit goes into and is held; this B subunit ring is capable of binding to a receptor a glycoprotein or a glycolipid, on the surface of the host cell. Without the B subunits, the A subunit has no way of attaching to or entering the cell, thus no way to exert its toxic effect. Cholera toxin, shiga toxin, SubAB toxin all have B subunits that are made up of five identical protein components, meaning that their B subunits are homopentamers. Pertussis toxin is different where its pentameric ring is made up of four different protein components, where one of the components is repeated to form a heteropentamer. Cholera toxin, pertussis toxin, shiga toxin all have their targets in the cytosol of the cell. After their B subunit binds to receptors on the cell surface, the toxin is enveloped by the cell and transported inside either through clathrin-dependent endocytosis or clathrin-independent endocytosis.
For the cholera toxin, the principal glycolipid receptor for the cholera toxin is ga