New strains of Vibrio cholerae

M. Madan Babu and Dr. K. Sankaran, Center for Biotechnology, Anna University

CHOLERA AFFECTS millions, in endemic areas and causes thousands of deaths especially during seasonal epidemics. Robert Koch, the famous microbiologist of Germany, discovered Vibrio cholerae, the causative organism. Because of its characteristic shape he originally referred to it as comma bacilli. Nearly 7-8 epidemics caused by the pathogen `Vibrio cholerae affected different parts of the world. Last one was in 1992 in Chennai and other eastern parts of India.

The causative organism was found to be different from the already known 138 different serotypes of V. cholerae and therefore was referred to as O139. V. cholerae is a water borne curved-rod-shaped gram-negative bacterium, measuring 0.3 micron (micron is one thousandth of a millimetre) in diametre and 1.3 micron in length. It has a single flagellum at one end for its motility. When viewed under an electron microscope at a magnification of 50,000 times, fine hair-like structures called pili are seen on its body. These structures are used to establish contact with host cells. In case of pathogens like V. cholerae there are special pili that offer specific advantages to colonise effectively. (Colonization is an essential attribute for a pathogen to be able to establish itself in a foreign host before infection.) Though a few pili have been implicated in the process, all the components necessary for a attachment of V. cholerae to the intestinal cells have not yet been identified.

However, once attached to the small intestine, V. cholerae grows luxuriantly in an alkaline environment in the presence of bile salts, a condition prevailing in our small intestine. After successfully colonising in the intestine, overcoming the peristaltic movement and other host defence mechanisms, it secrets a large amount of the cholera toxin or choleragen, that is responsible for the diarrhoea. Cholera toxin is a protein. The infection by the cholera toxin finally leads to expulsion of sodium chloride from the body along with 10-12 litres of water in a day. This leads to dehydration and death.

It was only in 1996 Matthew K. Waldor and John J. Mekalanos of the U.S. reported a stunning discovery about the toxin. The toxin was for the first time shown to be not a part of the bacterium but actually that of a virus ( a virus that infects a bacterium is called a bacteriophage) that got integrated into the V. cholerae genome. Normally this virus remains silent within V. cholerae but during infection it gets activated.

It then multiplies within the bacterium and escapes to infect other V. cholerae cells. Under certain laboratory conditions it is possible to activate and release this virus or phage from V. cholerae. It is called CTX phage, CT standing for cholera toxin. Along with the toxin, a specific pilus called toxin-corregulated pilus (TCP) is also produced on the surface of V. cholerae.

The released phages specifically attach to it and enter into the bacterium. Vigorous viral multiplication results in the production of large amounts of toxin causing severe diarrhoea. About 150 different strains of V. cholerae have been found. A few, belonging to the serotype 01 are virulent human pathogens. It has been intriguing as to how only some strains of V. cholerae are virulent and how they survive between seasonal epidemics. The recent discovery of the toxin carrying phage is helping us to understand this mechanism. It is quite possible that new strains arise like when the phage infects a Vibrio strain that may have the pilus but no toxin.

Another research finding is that the pilus is also of viral origin and therefore can be acquired from another phage infection. thus a virulent cholera pathogen can be born from a totally avirulent strain.

It is also possible that multiple copies of the viral genome within the cholera pathogen can generate more virulent forms similar to the one causing the eighth pandemic. Another dangerous trend noticed in recent years in some clinical isolates of V. cholerae is the acquisition of resistance to common antibiotics, thus rendering them useless in controlling the pathogen.

In the light of these recent findings the frightening prospect of fighting never forms of V. cholerae in the future might become real. The more we understand about this pathogen, less likely it appears that it could be eradicated. Therefore, we have to fall back on personal and public hygiene to keep these deadly pathogens away.

M. Madan Babu & K. Sankaran

Centre for Biotechnology,
Anna University, Chennai.