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Formula | C16H13NO4 |
Molar mass | 283.283 g·mol−1 |
3D model (JSmol) | |
Density | 1.40 g/cm3 |
Melting point | 180–183 °C (356–361 °F) |
Boiling point | 536.52 °C (997.74 °F) |
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Virstatin is a small molecule that inhibits the activity of the cholera protein, ToxT. [1]
Its activity in cholera was first published in 2005 in a paper that described the screening of a chemical library in a phenotypic screen and subsequent testing of one of the hits in infected mice. [1] [2]
The compound is an isoquinoline alkaloid [3] and can be synthesized by a simple two-step synthesis [4]
Cholera is an infection of the small intestine by some strains of the bacterium Vibrio cholerae. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Vomiting and muscle cramps may also occur. Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance. This may result in sunken eyes, cold skin, decreased skin elasticity, and wrinkling of the hands and feet. Dehydration can cause the skin to turn bluish. Symptoms start two hours to five days after exposure.
Vibrio cholerae is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera, which can be derived from the consumption of undercooked or raw marine life species or drinking contaminated water.
El Tor is a particular strain of the bacterium Vibrio cholerae, the causative agent of cholera. Also known as V. cholerae biotype eltor, it has been the dominant strain in the seventh global cholera pandemic. It is distinguished from the classic strain at a genetic level, although both are in the serogroup O1 and both contain Inaba, Ogawa and Hikojima serotypes. It is also distinguished from classic biotypes by the production of hemolysins.
Vibrio is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to survive in fresh water, Vibrio spp. are commonly found in various salt water environments. Vibrio spp. are facultative anaerobes that test positive for oxidase and do not form spores. All members of the genus are motile. They are able to have polar or lateral flagellum with or without sheaths. Vibrio species typically possess two chromosomes, which is unusual for bacteria. Each chromosome has a distinct and independent origin of replication, and are conserved together over time in the genus. Recent phylogenies have been constructed based on a suite of genes.
The Vibrionaceae are a family of Pseudomonadota given their own order, Vibrionales. Inhabitants of fresh or salt water, several species are pathogenic, including the type species Vibrio cholerae, which is the agent responsible for cholera. Most bioluminescent bacteria belong to this family, and are typically found as symbionts of deep-sea animals.
Noscapine is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects.
Vibrio parahaemolyticus (V. parahaemolyticus) is a curved, rod-shaped, Gram-negative bacterial species found in the sea and in estuaries which, when ingested, may cause gastrointestinal illness in humans. V. parahaemolyticus is oxidase positive, facultatively aerobic, and does not form spores. Like other members of the genus Vibrio, this species is motile, with a single, polar flagellum.
Filamentation is the anomalous growth of certain bacteria, such as Escherichia coli, in which cells continue to elongate but do not divide. The cells that result from elongation without division have multiple chromosomal copies.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
Cholera toxin is an 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.
Bacterial small RNAs are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.
The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA).
Interspecies quorum sensing is a type of quorum sensing in which bacteria send and receive signals to other species besides their own. This is accomplished by the secretion of signaling molecules which trigger a response in nearby bacteria at high enough concentrations. Once the molecule hits a certain concentration it triggers the transcription of certain genes such as virulence factors. It has been discovered that bacteria can not only interact via quorum sensing with members of their own species but that there is a kind of universal molecule that allows them to gather information about other species as well. This universal molecule is called autoinducer 2 or AI-2.
The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda.
VqmR small RNA was discovered in Vibrio cholerae, a bacterium which can cause cholera, using differential RNA sequencing (sRNA-seq) under conditions of low and high cell density which were being used to study quorum sensing (QS). QS controls virulence and biofilm formation in Vibrio cholerae; it has been shown previously that it is directed by the Qrr sRNAs. VqmR has been shown to repress the expression of multiple mRNAs including the rtx toxin genes and the vpsT, which is required for biofilm formation. In fact, VqmR which is highly conserved in vibrionaceae, was shown to strongly inhibit biofilm formation by repressing the vpsT gene; it could be the link between biofilm formation and QS.
Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.
John Mekalanos is a microbiologist who is primarily known for leading one of the first teams that reported the discovery of the type VI secretion system as well as his work on the pathogenicity of the bacterial species Vibrio cholerae, its toxin, and its secretion systems. Since 1998, he has been a member of the National Academy of Sciences.
Melanie Blokesch is a German microbiologist. Her research focuses on Vibrio cholerae, the bacterium causing cholera. She is a professor of life sciences at École Polytechnique Fédérale de Lausanne (EPFL), where she heads the Laboratory of Molecular Microbiology.
Virginia L. Miller is a microbiologist known for her work on studying the factors leading to disease caused by bacteria. Miller is an elected fellow of the American Academy of Microbiology (2003) and a former Pew Charitable Trust Biomedical Scholar (1989).
Jan Roland Holmgren is a Swedish physician, microbiologist, immunologist, and vaccinologist, known for his research on cholera and mucosal immunology, specifically, for his leadership in developing "the world's first effective oral cholera vaccine".