Vibrio cholerae Cholera

Morphology and culture. Cholera vibrios are Gram-negative rod bacteria, usually slightly bent (comma-shaped), 1.5-2 im in length, and 0.3-0.5 im wide, with monotrichous flagellation (Fig. 4.19).

Culturing of V. cholerae is possible on simple nutrient mediums at 37 °C in a normal atmosphere. Owing to its pronounced alkali stability, V. cholerae can be selectively cultured out of bacterial mixtures at pH 9.

Antigens and classification. V. cholerae bacteria are subdivided into serovars based on their O antigens (lipopolysaccharide antigens). The serovar pathogen is usually serovar O:1. Strains that do not react to an O:1 antiserum are grouped together as nonO:1 vibrios. NonO:1 strains were recently described in India (O:139) as also causing the classic clinical picture of cholera. O:1 vibrios are further subclassified in the biovars cholerae and eltor based on physiological characteristics. The var eltor has a very low level of virulence.

Cholera toxin. Cholera toxin is the sole cause of the clinical disease. This substance induces the enterocytes to increase secretion of electrolytes, above all Cl- ions, whereby passive water loss also occurs. The toxin belongs to the group of AB toxins (see p. 16). Subunit B of the toxin binds to enterocyte receptors, the active toxin subunit A causes the adenylate cyclase in the enterocytes to produce cAMP continuously and in large amounts (Fig. 4.20). cAMP in turn acts as a second messenger to activate protein kinase A, which then activates the specific cell proteins that control secretion of electrolytes. The toxin genes ctxA and ctxB are components of the so-called CTX element, which is integrated in the nucleoid of toxic cholera vibrios (see lysogenic conversion, p. 186) as part of the genome of the filamentous prophage CTXf. The CTX element also includes several regulator genes that regulate both produc-

Fig. 4.19 Comma-shaped rod bacteria with monotrichous flagellation (SEM image).

Monotrichous
4

— Mechanism of Action of Cholera Toxin

— Mechanism of Action of Cholera Toxin

Vibrio Cholerae Toxin Coregulated Pilus
inactivates the GTPase activity of Gsa by means of ADP-ribosylation o
Vibrio Cholerae Cell Invasion

Fig. 4.20 Cholera toxin disrupts the Gs protein-mediated signal cascade.

1 The Gs proteins in the membrane comprise the three subunits a, b, and y. GDP is bound to subunit a. Gs is inactive in this configuration.

2 After a signal molecule is bound to the membrane receptor R, the subunits dissociate from Gs; also, the GDP on the Gsa is phosphorylated to GTP.

3 Gsa-GTP then combines with adenylate cyclase to form the active enzyme that transforms ATP into the second messenger cAMP.

4 When the signal molecule once again dissociates from the receptor, the GTP bound to the Gsa is dephosphorylated to GDP, i.e., inactive status is restored. This is the step that cholera toxin prevents: the A, subunit of the cholera toxin (CTA,) catalyzes ADP-ribosylation of Gsa, which thus loses its GTPase activity so that the adenylate cyclase is not"switched off" and synthesis of cAMPcontinues unchecked.

Fig. 4.20 Cholera toxin disrupts the Gs protein-mediated signal cascade.

1 The Gs proteins in the membrane comprise the three subunits a, b, and y. GDP is bound to subunit a. Gs is inactive in this configuration.

2 After a signal molecule is bound to the membrane receptor R, the subunits dissociate from Gs; also, the GDP on the Gsa is phosphorylated to GTP.

3 Gsa-GTP then combines with adenylate cyclase to form the active enzyme that transforms ATP into the second messenger cAMP.

4 When the signal molecule once again dissociates from the receptor, the GTP bound to the Gsa is dephosphorylated to GDP, i.e., inactive status is restored. This is the step that cholera toxin prevents: the A, subunit of the cholera toxin (CTA,) catalyzes ADP-ribosylation of Gsa, which thus loses its GTPase activity so that the adenylate cyclase is not"switched off" and synthesis of cAMPcontinues unchecked.

tion of the toxin and formation of the so-called toxin-coregulated pili (TCP) on the surface of the Vibrio cells.

Pathogenesis and clinical picture. Infection results from oral ingestion of the pathogen. The infective dose must be large (-108), since many vibrios are killed by the hydrochloric acid in gastric juice. Based on their pronounced stability in alkaline environments, vibrios are able to colonize the mucosa of the proximal small intestine with the help of TCP (see above) and secrete cholera toxin (see Fig. 4.20). The pathogen does not invade the mucosa.

The incubation period of cholera is two to five days. The clinical picture is characterized by voluminous, watery diarrhea and vomiting. The amount of fluids lost per day can be as high as 20 l. Further symptoms derive from the resulting exsiccosis: hypotension, tachycardia, anuria, and hypothermia. Lethality can be as high as 50% in untreated cases.

Diagnosis requires identification of the pathogen in stool or vomit. Sometimes a rapid microscopical diagnosis succeeds in finding numerous Gram-negative, bent rods in swarm patterns. Culturing is done on liquid or solid selective mediums, e.g., alkaline peptone water or taurocholate gelatin agar. Suspected colonies are identified by biochemical means or by detection of the O:1 antigen in an agglutination reaction.

Therapy. The most important measure is restoration of the disturbed water and electrolyte balance in the body. Secondly, tetracyclines and cotrimoxa-zole can be used, above all to reduce fecal elimination levels and shorten the period of pathogen secretion.

Epidemiology and prevention. Nineteenth-century Europe experienced several cholera pandemics, all of which were caused by the classic cholerae bio-var. An increasing number of cases caused by the biovar eltor, which is characterized by a lower level of virulence, have been observed since 1961. With the exception of minor epidemics in Italy and Spain, Europe, and the USA have been spared major outbreaks of cholera in more recent times. South America has for a number of years been the venue of epidemics of the disease.

Humans are the only source of infection. Infected persons in particular eliminate large numbers of pathogens. Convalescents may also shed V. cholerae for weeks or even months after the infection has abated. Chronic carriers as with typhoid fever are very rare. Transmission of the disease is usually via foods, and in particular drinking water. This explains why cholera can readily spread to epidemic proportions in countries with poor hygiene standards.

Protection from exposure to the pathogen is the main thrust of the relevant preventive measures. In general, control of cholera means ensuring adequate food and water hygiene and proper elimination of sewage. In case of an outbreak, infected persons must be isolated. Infectious excreta and contaminated objects must be disinfected. Even suspected cases of cholera must be reported to health authorities without delay. The incubation period of the cholera vibrio is reported in international health regulations to be five days. A vaccine containing killed cells as well an attenuated live vaccine are available. The level of immunization protection is, however, incomplete and lasts for only six months.

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Responses

  • berhane
    Why electrolytes are essential in agglutination reaction?
    7 years ago
  • tiina
    How agglutination reaction can identify serovars and biovars of Vibrio Cholera?
    6 years ago
  • Concordia
    How does vibrio cholera disrupts adrenal cyclase?
    6 years ago

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