Vibrio cholerae is a known cholera causing agent. Cholera is one of the lives threatening diarrheal infection which occurs in many countries especially the developing countries in Africa, Latin America and Asia. Cholera disease spreads in explosive epidemics and it affects a very large number of people. The epidemic's toxigenic strains can also spread across many countries and continents over a period of time leading to cholera pandemics. Although the Vibriocholera is a human pathogen, the bacteria forms part of aquatic flora found in brackish and estuarine waters. The Vibriogenus comprises of many bacterial species such as Vibrioparahaemolyticus, Vibriocholera and Vibriovulnificus. These are the most important human pathogens. Among the known subgroups of cholera, 0139 and 01 are the only two subgroups that cause cholera. On the other hand, the Vibrio cholerae that belong to other sub groups apart from these two occasionally cause extra intestinal illnesses or gastrointestinal illnesses by using different or similar virulence mechanisms.
The Vibriocholera 01 belongs to two main serotypes referred to as Inaba and Ogawa which are further categorized into two biotypes called el to and classical based on specific bio-chemical properties. Finally, there are additional genetic variations within 0139 and 01 that determine the phage resistance, antibiotic resistance and the phenotypes that are in some cases linked to the environmental fitness (Nair, B, G & Faruque, M, S. Pg 1). Historically, the first cholera pandemic started in the year 1817 and it spread outside the Indian subcontinent to the west and to southern Russia along the trade routes. The most extensive cholera pandemic which spread over a large geographical area started in the year 1961 and it exists today (Maira, F & Dartmouth College. Immunology and microbiology. Pg 2). This essay discusses various aspects of Vibrio cholerae.
Life cycle of Vibrio cholerae
The Vibrio cholerae bacteria is found in aquatic environment i.e. in marine and fresh water habitats in a biofilm state that attached to various surfaces or as free living organisms. When the human beings are infected with the contaminated food or water, the Vibrio cholerae bacteria that are able to survive the barrier of the gastric acid enters the small intestine which has a favorable colonization environment. While in the small intestines, the bacteria produces some colonization factors that assists in their epithelial attachment. They then produce TCP that facilitates the formation of micro colony which is required for intestinal epithelium colonization. During colonization, the bacteria produces CT which is a bipartite toxin consisting of five identical B subunits and an active A subunit.
The CT binds to the GMI receptor found on the epithelial cells through a B subunit referred to as pentameric. When the A subunit enters the epithelial cell, it is reduced into two subunits namely A1 and A2. The A1 subunit constitutively activates the G regulatory protein and leads to an activation of the adenylate cyclase leading to an increase in the cyclic AMP levels. The increased AMP activates the AMP dependent protein called kinase A which in turn phosphorylates and activate the proteins that are involved in the secretion of bicarbonate, chloride ions and water into the lumen. This result to severe diarrhea and the bacteria is disseminated back into the aquatic environment (Maira, F & Dartmouth College. Immunology and microbiology. Pg 4).
The molecular basis of the Vibrio cholerae survival in aquatic environment
While in the aquatic environment, the bacteria is associated with various which includes the phytoplankton mucilaginous surfaces such as cyanobacteria and zooplankton chitinous surfaces such as the copepods. The attachment to these surfaces enhances the survival of the bacterium in the environment through the provision of nitrogen and carbon. The formation of the biofilm prevents the tidal currents dilution. The Vibrio cholerae 0139 subgroup and the EL Tor biotype expresses a mannose sensitive haemagglubin type IV pilus. This is involved in the adherence to the zooplankton chitin. Also, the chitin regulated type IV is implicated in the surface adherence conferring a growth advantage to the Vibriocholera on the surfaces. The bacteria also expresses GbpA protein which binds to the GlcNAc sugar which is a chitin constituent and a common modification of the glycoproteins and lipids that are located on the epithelium of the intestines. Therefore, the GbpA assists in the bacteria's attachment to the zooplankton and it is also important for the efficient intestinal colonization (Maira, F & Dartmouth College. Immunology and microbiology. Pg 6).
Pathogenesis of Vibrio cholerae
The cholera's pathogenesis is a complex process that involves many virulence factors which assists the bacteria/pathogen in its movement to the small intestine's epithelium, colonization of the epithelium and in the production of an enteroroxin that disrupts the transportation of ions by the epithelial cells of the intestine. Therefore, the capability of the Vibrio cholerae strains to cause infections is dependent on their virulence gene contents which are different between the non-pathogenic land pathogenic strains. There are two important virulence factors in the Vibrio cholerae namely cholera toxin/CT and the toxin coregulated pilus/TCP. The cholera toxin is responsible for acute diarrhea while the rather is a colonization factor. The Vibrio cholerae infection starts with the ingestion of contaminated water or food that contains the organism.
After the passage to the human stomach, the Vibriocholera colonizes the small intestine using the TCP and produces CT which is responsible for disease manifestation. The CT acts as a classical A-B type toxin leading to ribosylation of ADP of a small G protein and the activation of tha adenylate cyclase giving rise to the high levels of the cyclic AMP within the host cells. This results to the production of many chloride irons and water from the human intestinal cells that result to diarrhea and vomiting. The massive outpouring of the electrolytes and water leads to very severe electrolyte abnormalities, metabolic acidosis and dehydration. Due to the fact that the environmental reservoir for the Vibrio cholerae is aquatic, its movement and passage through the acid barrier in the stomach and the subsequent colonization of the intestine has a highly regulated process and the expression of the several extra genes that are crucial for the survival and adaptation of the bacterium in the gastrointestinal environment. However, the responsibilities of the accessory virulence factors in cholera organisms are not well established (Nair, B, G & Faruque, M, S. Pg 2).
Clinical presentation, treatment, and vaccine development
Severe dehydration is the main symptom of cholera infection. When the Vibrio cholerae colonizes the small intestine, the virulence factors are produced and the cholera toxin is extracellularly secreted. The CT enters into the epithelial cell and causes a series of events that involves the upregulation of adenylate cyclase which is the increased cAMP concentrations. This leads to the inhibition of the absorption of sodium ions by the villi of the small intestines and the secretion of bicarbonate and chloride to the intestinal lumen increases. The change of the concentration of electrolyte in the lumen leads to the increased influx of water from the epithelial cells of the intestines to restore the osmotic balance. Dehydration in some patients is exacerbated by the vomiting onset which sometimes presents a barrier to oral dehydration therapies. Dehydration causes some physical changes such as skin turgor, sunken cheeks and eyes, dry mucus membranes and deep respirations increase. In addition, it causes increased pulse rate and blood pressure and reduction of blood volume.
The treatments of cholera infections are done to especially prevent the dehydration from progressing to more severe state and symptoms. If the dehydration becomes more severe and the taking of oral fluids becomes impossible, the utilization of rehydration of electrolytes and water is necessary. Sometimes, the fluid rehydration using ORT (oral rehydration therapy) solution is sufficient. The oral rehydration therapy solution is the water that is supplemented with glucose and electrolyte concentration and it utilizes the cholera toxin glucose mediated co-transport of sodium and water to re-establish the electrolyte balance within the epithelial cells (Jude, A. B & Dartmouth College. Immunology and microbiology. Pg 8).
The use of vaccines can also shorten the length of the symptoms that the cholera patients suffer. Currently, the vaccines for protection of people in the endemic areas are being developed. These vaccines' strategies includes a killed cell that consists of the 01 strains in addition to the purified cholera toxin B subunit as well as the lyophilized oral vaccine that is based on the avirulent V. cholerae mutant CVD103-HgR classical 01 derivative. Although a wide range of protection without side effect have been observed in the vaccines, the subunit vaccines are currently developed which are able to give a longer lasting protection as compared to the earlier vaccines. Finally, the cholera infections continues to be a threat in some parts of Africa and asia and it is estimated that about 300000 cholera cases were reported to the World Health Organization from 1995 to 2004 and this has been on the increase since 2004 (Jude, A. B & Dartmouth College. Immunology and microbiology. Pg 9).
The antibiotic resistance in Vibrio cholerae
Antibiotics are defined as the chemical compounds that are able to inhibit the growth of organisms more especially the bacteria. These substances are integral components of the modern society that are tied to human activities (Thomson, K. F & Old Dominion University, Pg 5). The resistance to antibiotics has been observed in a wide range of bacteria species such as the Vibrio cholerae. The researchers once thought that the Vibrio cholerae lacked the ability of retaining the resistance plasmids. The discovery of the resistant strains that are associated with the epidemics since late 1970s has since disapproved the idea. The strains have been isolated with the plasmid-encoded high level resistance to tetracycline, kanamycin, streptomycin and sulfonamides among others.
The persistent appearance and disappearance of the strains that are resistant to the antibiotic action implies an extensive pool of the antibiotic-resistance genes in the populations of the Vibrio cholerae. For instance, the V. cholerae 0139 is resistant to streptomycin and sulfamethoxazole-trimethoprim. Unlike other pathogens, the Vibrio cholerae strains revert to the sensitivity of the antibiotics even after the strains have become endemic to a certain region. This tendency can be traced to a fact that the Vibrio cholerae is associated primarily with the aquatic environment and it is only secondarily a human pathogen. Generally, there is less pressure for the Vibrio cholerae to maintain resistance to antibiotics in an environmental setting resulting to loss of the resistyant phenotypes in the populations of the Vibrio cholerae (Thomson, K. F & Old Dominion University. Pg 12).
In conclusion, the Vibrio cholerae is transmitted through the fecal-oral route and it exclusively occurs via contaminated food and water. The Vibrio cholerae bacteria are becoming resistant to antibiotics. Therefore, the continued researches and discoveries of the mechanisms that are utilized by the Vibrio cholerae during colonization in the intestines are needed for the making vaccine strategies that will be more effective.