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Adenylyl cyclase is an enzyme with key regulatory roles in essentially all cells. It is the most polyphyletic known enzyme: six distinct classes have been described, all catalyzing the same reaction but representing unrelated gene families with no known sequence or structural homology. The best known class of adenylyl cyclases is class III or AC-III. AC-III occurs widely in eukaryotes and has important roles in many human tissues.
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by weeks of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The coughing may last for 10 or more weeks, hence the phrase "100-day cough". A person may cough so hard that they vomit, break ribs, or become very tired from the effort. Children less than one year old may have little or no cough and instead have periods where they do not breathe. The time between infection and the onset of symptoms is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host-pathogen interface.
Bordetella bronchiseptica is a small, Gram-negative, rod-shaped bacterium of the genus Bordetella. It can cause infectious bronchitis in dogs and other animals, but rarely infects humans. Closely related to B. pertussis—the obligate human pathogen that causes pertussis ; B. bronchiseptica can persist in the environment for extended periods.
Bordetella is a genus of small, Gram-negative coccobacilli of the phylum Proteobacteria. Bordetella species, with the exception of B. petrii, are obligate aerobes, as well as highly fastidious, or difficult to culture. All species can infect humans. The first three species to be described ; are sometimes referred to as the 'classical species'. Two of these are also motile.
Alfred Goodman Gilman was an American pharmacologist and biochemist. He and Martin Rodbell shared the 1994 Nobel Prize in Physiology or Medicine "for their discovery of G-proteins and the role of these proteins in signal transduction in cells."
Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments, including hypertension, viral infection, and autoimmunity.
Bordetella pertussis is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough. Like B. bronchiseptica, B. pertussis is motile and expresses a flagellum-like structure. Its virulence factors include pertussis toxin, adenylate cyclase toxin, filamentous hæmagglutinin, pertactin, fimbria, and tracheal cytotoxin.
Cholera toxin is AB5 multimeric protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection. It is a member of the Heat-labile enterotoxin family.
Adenylate cyclase toxin is a virulence factor produced by some members of the genus Bordetella. Together with the pertussis toxin it is the most important virulence factor of the causative agent of whooping cough, Bordetella pertussis. Bordetella bronchiseptica and Bordetella parapertussis, also able to cause pertussis-like symptoms, also produce adenylate cyclase toxin. It is a toxin secreted by the bacteria to influence the host immune system.
Antoine Danchin is a French geneticist known for his research in several fields of biology, from the structure and function of adenylate cyclase, to modelisation of learning in the nervous system and the early development of genomics and bioinformatics. He is the Chairman of the startup AMAbiotics, specialised in metabolic bioremediation and synthetic biology. He was the director of the Department Genomes and Genetics at the Institut Pasteur in Paris where he headed the Genetics of Bacterial Genomes Unit.
Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene. PACAP is similar to vasoactive intestinal peptide. One of its effects is to stimulate enterochromaffin-like cells. It binds to vasoactive intestinal peptide receptor and to the PACAP receptor.
Bordetella parapertussis is a small Gram-negative bacterium of the genus Bordetella that is adapted to colonise the mammalian respiratory tract. Pertussis caused by B. parapertussis manifests with similar symptoms to B. pertussis-derived disease, but in general tends to be less severe. Immunity derived from B. pertussis does not protect against infection by B. parapertussis, however, because the O-antigen is found only on B. parapertussis. This antigen protects B. parapertussis against antibodies specific to B. pertussis, so the bacteria are free to colonize the host's lungs without being subject to attack by previous antibodies. These findings suggest B. parapertussis evolved in a host population that had already developed immunity to B. pertussis, where being able to evade B. pertussis immunity was an advantage.
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.
Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC1, is a protein that in humans is encoded by the ADCYAP1R1 gene. This receptor binds pituitary adenylate cyclase activating peptide.
Bordet-Gengou agar is a type of agar plate optimized to isolate Bordetella, containing blood, potato extract, and glycerol, with an antibiotic such as cephalexin or penicillin and sometimes nicotinamide. The potato extract provided nitrogen and vitamins, and potato starch absorbed fatty acids present in nasal secretions or collection-swab cotton that inhibited growth; glycerol was a carbon source. Medical Microbiology, 4th edition states that Regan-Lowe medium has replaced Bordet-Gengou medium as the medium of choice for routine Bordetella pertussis incubation.
The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.
Bifunctional hemolysin/adenylate cyclase is a protein that in B. pertussis is encoded by the cyaA gene. This protein in turn is cleaved into a calmodulin-sensitive adenylate cyclase (cyaA–ACD) and hemolysin. Both are virulence factors facilitating respiratory tract colonization by B. pertussis. The cyaA–ACD binds to a M2 integrin cell surface receptor and inserts its N-terminal adenylyl cyclase domain into the cytosol. After binding to calmodulin, cyaA–ACD catalyzes the cyclization of AMP into cAMP. This catalysis raises the intracellular concentration of cAMP to toxic levels.
Tracheal cytotoxin (TCT) is a 921 dalton glycopeptide released by Bordetella pertussis and Neisseria gonorrhoeae.
Eva Julia Neer (1937–2000) was an American physician, biochemist, and cell-biology scientist who gained U.S. national research awards for her discoveries on G-protein subunit structure and function. She described the physiological roles of these subunits as an integrated and versatile molecular system of signal transduction for membrane-receptor regulation of cell function. Her research concepts turned her into a world leader in G-protein studies and impinged widely on the general understanding of cell behavior.
References
- ↑ Kessin RH, Franke J (April 1986). "Secreted adenylate cyclase of Bordetella pertussis: calmodulin requirements and partial purification of two forms". J. Bacteriol. 166 (1): 290–6. PMC 214590 . PMID 2870055.
- ↑ Ladant D, Brezin C, Alonso JM, Crenon I, Guiso N (December 1986). "Bordetella pertussis adenylate cyclase. Purification, characterization, and radioimmunoassay". J. Biol. Chem. 261 (34): 16264–9. PMID 2877986.
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