page_title: Vibrio cholerae
section_title: Pathogenicity
hierarchical_section_title: Vibrio cholerae / Pathogenicity
caption_attribution_description: English: Toxin Svenska: Toxin
context_page_description: Vibrio cholerae is a Gram-negative, comma-shaped bacterium. The bacterium's natural habitat is brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and other shellfish. Some strains of V. cholerae cause the disease cholera, which can be derived from the consumption of undercooked or raw marine life species. V. cholerae is a facultative anaerobe and has a flagellum at one cell pole as well as pili. V. cholerae can undergo respiratory and fermentative metabolism. When ingested, V. cholerae can cause diarrhea and vomiting in a host within several hours to 2–3 days of ingestion. V. cholerae was first isolated as the cause of cholera in 1854 by Italian anatomist Filippo Pacini and by the Catalan Joaquim Balcells i Pascual in the same year, but their discovery was not widely known until Robert Koch, working independently 30 years later, publicized the knowledge and the means of fighting the disease.
context_section_description: V. cholerae pathogenicity genes code for proteins directly or indirectly involved in the virulence of the bacteria. To adapt the host intestinal environment and to avoid being attacked by bile acids and antimicrobial peptides, V. cholera used its outer membrane vesicles (OMVs). Upon entry, the bacteria sheds its OMVs, containing all the membrane modifications that make it vulnerable for the host attack. 
  During infection, V. cholerae secretes cholera toxin (CT), a protein that causes profuse, watery diarrhea (known as "rice-water stool"). This cholera toxin contains 5 B subunits that plays a role in attaching to the intestinal epithelial cells and 1 A subunit that plays a role in toxin activity. Colonization of the small intestine also requires the toxin coregulated pilus (TCP), a thin, flexible, filamentous appendage on the surface of bacterial cells. Expression of both CT and TCP is mediated by two component systems (TCS), which typically consist of a membrane-bound histidine kinase and an intracellular response element. TCS enable bacteria to respond to changing environments. In V. cholerae several TCS have been identified to be important in colonization, biofilm production and virulence. Recently, small RNAs (sRNA) have been identified as targets of V. cholerae TCS. Here, sRNA molecules bind to mRNA to block translation or induce degradation of inhibitors of expression of virulence or colonization genes. In V. cholerae the TCS EnvZ/OmpR alters gene expression via the sRNA coaR in response to changes in osmolarity and pH. An important target of coaR is tcpI, which negatively regulates expresion of the major subunit of TCP (TcpA). When tcpI is bound by coaR it is no longer able to repress expression tcpA, leading to an increased colonization ability. Expression of coaR is upregulated by EnvZ/OmpR at a pH of 6,5, which is the normal pH of the intestinal lumen, but is low at higher pH values. V. cholerae  in the intestinal lumen utilizes the TCP to attach to the intestinal mucosa, not invading the mucosa. After doing so it secretes cholerae toxin causing its symptoms. This then increases cyclic AMP or cAMP by binding (cholerae toxin) to adenylyl cyclase activating the GS pathway which leads to efflux of water and sodium into the intestinal lumen causing watery stools or rice watery stools.
  V. cholerae can cause syndromes ranging from asymptomatic to cholera gravis. In endemic areas, 75% of cases are asymptomatic, 20% are mild to moderate, and 2-5% are severe forms such as cholera gravis. Symptoms include abrupt onset of watery diarrhea (a grey and cloudy liquid), occasional vomiting, and abdominal cramps. Dehydration ensues, with symptoms and signs such as thirst, dry mucous membranes, decreased skin turgor, sunken eyes, hypotension, weak or absent radial pulse, tachycardia, tachypnea, hoarse voice, oliguria, cramps, kidney failure, seizures, somnolence, coma, and death. Death due to dehydration can occur in a few hours to days in untreated children. The disease is also particularly dangerous for pregnant women and their fetuses during late pregnancy, as it may cause premature labor and fetal death. A study done by the Centers for Disease Control (CDC) in Haiti found that in pregnant women who contracted the disease, 16% of 900 women had fetal death. Risk factors for these deaths include: third trimester, younger maternal age, severe dehydration, and vomiting Dehydration poses the biggest health risk to pregnant women in countries that there are high rates of cholera.  In cases of cholera gravis involving severe dehydration, up to 60% of patients can die; however, less than 1% of cases treated with rehydration therapy are fatal. The disease typically lasts 4–6 days. Worldwide, diarrhoeal disease, caused by cholera and many other pathogens, is the second-leading cause of death for children under the age of 5 and at least 120,000 deaths are estimated to be caused by cholera each year. In 2002, the WHO deemed that the case fatality ratio for cholera was about 3.95%.
caption: Cholera toxin interrupting regulation of adenyl cyclase inside the cell causing efflux of water and sodium into the intestinal lumen.
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