Pathogenesis

Vibrio cholerae is killed by acid, and so large numbers must be ingested before enough survive stomach passage to establish infection. The organisms adhere to the small intestinal epithelium by means of pili and other surface proteins. The organisms multiply on the epithelial cells (figure 24.12) but do no visible damage to them. The bacteria, however, produce the potent exotoxin, cholera toxin, which is responsible for the symptoms of cholera. As with a number of other bacterial exotoxins, cholera toxin is heat-labile, and its protein molecule is composed of two parts, A and B, a classic A-B toxin (figure 24.13). As in all such toxins,

24.5 Bacterial Diseases of the Lower Alimentary System 611

10 mm

Figure 24.12 Scanning Electron Micrograph of Vibrio cholerae Attached to Small Intestinal Mucosa Attachment occurs by means of pili.

10 mm

Figure 24.12 Scanning Electron Micrograph of Vibrio cholerae Attached to Small Intestinal Mucosa Attachment occurs by means of pili.

the B fragment has no toxic activity but serves to bind the toxin, irreversibly in this case, to specific receptors on the microvilli of the epithelial cells. The A fragment, responsible for toxicity, causes the activation of the enzyme adenylate cyclase, which converts ATP to cyclic adenosine monophosphate (cAMP). This is another example of ADP ribosylation, in which a toxin causes the ADP ribose part of nicotinamide adenine dinucleotide (NAD) to react with a cellular target. In this case, the target of the toxin is a regulatory substance called a G protein that under normal conditions switches back and forth from active to inactive forms to regulate adenylate cyclase activity and, therefore, fluid secretion. ADP ribosylation of this G protein makes it permanently active, thus causing maximal cAMP production by the cell. Accumulation of cAMP in the intestinal cells converts them into little pumps that continuously secrete chloride ions accompanied by other electrolytes and water from the blood into the intestine. Although the large intestine is not affected by the toxin, it cannot absorb the huge volume of fluid that rushes through it, and diarrhea results. Over time, the normal shedding of intestinal cells gets rid of the toxin. ■ A-B toxins, p. 472 ■ NAD, p. 134

In mid-1996, scientists at Harvard Medical School showed that cholera toxin was encoded by a filamentous bacteriophage that infects V. cholerae via the same pili by which the bacteria attach themselves to the intestinal cells. Synthesis of both cholera toxin and the pili is regulated by the same bacterial gene, so that both toxin and pili, the two factors required for disease production, are synthesized simultaneously. Synthesis of cholera toxin by lysogenic V. cholerae is another example of lysogenic conversion. ■ lysogenic conversion, p. 331

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Bacterial Vaginosis Facts

Bacterial Vaginosis Facts

This fact sheet is designed to provide you with information on Bacterial Vaginosis. Bacterial vaginosis is an abnormal vaginal condition that is characterized by vaginal discharge and results from an overgrowth of atypical bacteria in the vagina.

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