Opening a new door to an effective vaccine and therapy for a disease that strikes thousands annually, researchers at Dartmouth Medical School discovered that the bacteria that causes the intestinal disease Cholera spreads in the environment in much the same way it infects humans.
The study investigates the bacterium Vibrio cholerae and its ability to attach to a host, enabling it to multiply and adding to the risk of infecting humans.
"We've discovered, through genetics, a factor that is important in the normal biology of the organism out in the environment and it is also one of the very initial factors for cholera colonization in the intestine," said Dr. Ronald Taylor, professor of microbiology and immunology at DMS who led the research. "Now that we know what the bacterium attaches to in the intestine, we can find ways to block that initial contact."
Cholera and the bacterium that causes it is found in contaminated drinking water and food, often in underdeveloped countries and refugee camps. Once the disease takes hold, it causes diarrhea, vomiting, severe dehydration and can result in death if treatment is not promptly given. In 2001 alone, 28 countries reported over 40 outbreaks of cholera to the World Health Organization, resulting in the deaths of thousands.
Large outbreaks are often traced back to contaminated water supplies that are commonly associated with algal or zooplankton blooms. For the V. cholerae bacterium to infect someone with cholera, the bacterium often binds to plankton in the aquatic environment before it arrives at the human intestine via contaminated food and water sources. V. cholerae attaches to the outer surface of plankton, made up of a carbonate substance called chitin. Once attached to the plankton's chitin, the bacterium thrives on the carbon and multiplies. Humans do not have chitin in the surface of intestinal cells, where the bacterium takes hold, and researchers have been searching for another substance that could be responsible for playing a role in attachment.
In the study, Taylor and colleagues screened cultured intestinal cells and found mutant bacteria that had trouble binding to the intestinal cells. One mutant strain of V. cholerae lacks a gene that enables it to properly bind with a sugar called GlcNAc. When they compared it with normal, wild-type V. cholerae bacteria, the researchers found that the protein encoded by this gene provided normal bacteria the ability to attach to the GlcNAc on cells. The team verified that the GlcNAc in the intestine initiates the attachment and colonization of the bacteria by testing the mutant strain on zooplankton and cultured intestinal cells in vitro as well as in an in vivo cholera model.