Posted by: David Walsh14 JAN 2015
Since the first of its six great pandemics in the early 19th century, cholera, caused by the bacterium Vibrio cholera, has claimed the lives of hundreds of millions of victims. Confined for centuries in the Ganges delta area of India, the disease was spread to Europe and Central Asia, firstly by religious pilgrims, and later by British troops. The connection between the disease and contaminated water was first made in 1854, by the physician John Snow, when he linked a cholera outbreak in Soho to a water pump in nearby Broad Street. The earliest reference to the disease appears in Sanskrit writings from 430BC, where it is described as a disease that kills “by draining water from its victims”, a reference to the watery stools characteristic of the disease. There are up to five million cases of cholera each year, and between 100,000-120,000 deaths. Victims can lose up to 40 litres of fluid in just a few days.
The standard treatment is oral rehydration therapy, consisting of water, electrolytes, and glucose. Mortality from the disease is as high as 50% without treatment, but this drops to around 1% with rehydration therapy. The purpose of the glucose in the rehydration mix is to provide a source of carbon, which helps the intestine absorb the salts more efficiently. However, it has been suggested that in some instances the glucose may also provide a substrate for the Vibrio bacterium, increasing its toxicity, and field studies have suggested that other more complex sources of starch, such as rice or potato powder may be more effective, as the pathogen is not able to utilise these as carbon sources.
In a very recent study, published in the January 2015 edition of Science, researchers in Lausanne have described how V. cholera uses a tiny spear-like device, known as the “type VI secretion system”, to kill other bacteria and steal their genetic material. Activation of the device is triggered by the bacterium’s environment. In the sea, V. cholera attaches to the surface of crustaceans, where it feeds on chitin from their shells. When chitin is available, the bacterium enters its aggressive mode, attacking neighbouring bacteria with its “spear”. This has the effect of not only killing them, but it can also lead to so-called horizontal gene transfer, whereby the V. cholera bacterium harvests sections of genetic material from its victim. This has been shown to have the potential to make the bacterium more resistant to environmental threats, or even to antibiotics.
Colonisation of the human intestine by pathogenic bacteria is difficult, and V. cholera has developed a variety of means to overcome the competition of billions of other micro-organisms that make up the normal gut flora. Studies examining the entry and colonisation of the intestines by V. cholera have demonstrated that the bacterium senses a temperature shift when it enters the human body, through a so-called ribonucleic acid thermometer. This has the effect of turning on virulence factors, such as the cholera toxin, that cause the disease. V. cholera then gains a foothold by harvesting and consuming a sugar, called sialic acid, from the surface of human cells lining the gut. It has been shown that the pathogen uses a form of active transport called a TRAP transporter to recognise sialic acid and facilitate its uptake in to the cell. Work is being done on methods of interfering with both the RNA thermometer, as well as the TRAP transporter, in the hope of developing therapies to reduce the still significant mortality rate from this disease.
1. S. Borgeaud, L. C. Metzger, T. Scrignari, M. Blokesch. The type VI secretion system of Vibrio cholerae fosters horizontal gene transfer. Science, 2015; 347 (6217): 63 DOI: 10.1126/science.1260064
2. Christopher Mulligan, Andrew P. Leech, David J. Kelly and Gavin H. Thomas. The Membrane Proteins SiaQ and SiaM Form an Essential Stoichiometric Complex in the Sialic Acid Tripartite ATP-independent Periplasmic (TRAP) Transporter SiaPQM (VC1777–1779) from Vibrio cholera. The Journal of Biological Chemistry, Vol. 287, Issue 5, 3598-3608 DOI: 10.1074/jbc.M111.281030 jbc.M111.281030
3 G. G. Weber, J. Kortmann, F. Narberhaus, K. E. Klose. RNA thermometer controls temperature-of Sciences, 2014; DOI: 10.1073/pnas.1411570111
4. Juliane Kühn, Flavio Finger, Enrico Bertuzzo, Sandrine Borgeaud, Marino Gatto, Andrea Rinaldo, Melanie Blokesch. Glucose- but Not Rice-Based Oral Rehydration Therapy Enhances the Production dependent virulence factor expression in Vibrio cholerae. Proceedings of the National Academy of Virulence Determinants in the Human Pathogen Vibrio cholerae. PLoS Neglected Tropical Diseases, 2014; 8 (12): e3347 DOI: 10.1371/journal.pntd.0003347