Cholera has been around for many centuries, but the disease came to prominence in the 1800s. While it may be a term that reminds us of another time in history, it is still very relevant today.
Today, an estimated 1.3 to 4 million people around the world are diagnosed with cholera each year, and as many as 143,000 people die from it, according to the Centers for Disease and Prevention.
Cholera, a diarrheal illness caused by infection of the intestine with Vibrio cholerae bacteria, can produce symptoms ranging from mild to life-threatening. People can rapidly lose body fluids, which can lead to dehydration and shock.
The people at the highest risk for cholera are those who live in places with unsafe drinking water, poor sanitation and inadequate hygiene.
The treatment for cholera includes immediate replacement of fluids and salts, intravenous fluid replacement and even antibiotics to shorten the course or diminish the severity of the illness. Without treatment, death can occur within hours.
In 2022, 29 countries reported cholera cases, and Haiti, Malawi, Yemen and Syria experienced major outbreaks. The increase in cases worldwide has grown in recent years, becoming more widespread and serious due to floods, droughts and massive migration caused by climate change.
Armed conflicts and natural catastrophes also limit clean drinking water and facilitate the spread of disease.
This year alone, the global resurgence of cholera sounded the alarm in the World Health Organization and the United Nation’s Children Fund (UNICEF).
Researching how cholera works in the body
Understanding what triggers a disease is vital for identifying new treatments. Fortunately, an international team of researchers – led by Eric Kurkonis at University of Detroit Mercy – have set their sights on doing just that. The long-term goal is to one day find a better way of treating cholera.
“The key Vibrio cholerae virulence gene activator ToxR has been studied for years by various laboratories, but how exactly it engages DNA has been a bit of a mystery,” Krukonis said.
Krukonis said he saw the effects of cholera on a community when he visited Kolkata, India, in 2008, during the fall monsoon and flooding season. The trip was part of an NIH-organized first training mission on Cholera Collaborative Research and Case Management.
“There were so many people coming into hospitals with severe dehydration,” he said. “That’s when I really started looking into the structure of regulators of cholera toxin expression with the hope of designing targeted therapeutics in the future.”
Krukonis’s Detroit Mercy team collaborated with researchers led by Miquel Coll at the Institute of Research in Biomedicine (IRB Barcelona) and the Institute of Molecular Biology Barcelona (IBMB-CSIC) in Spain.
Scientists have used various methods to test their hypotheses. Krukonis said the study they’ve been conducting has provided some explanation as to how cholera works. Coll said the study revealed that a protein binds to various regulatory sequences in bacterial DNA. In turn, this recruits RNA polymerase, the molecular machine that transcribes genes.
The team identified the atomic structure of the protein that’s bound to the DNA of two promoters of genes that control the virulence of Vibrio cholerae, which causes cholera. Essentially, a protein binds and activates genes that cause, among other effects, the production of the cholera toxin.
“This toxin causes severe diarrhea and consequent dehydration, which can be fatal in a few days if left untreated,” Coll said.
The findings from the research team are the first of its kind.
With this new information, researchers hope the next step will be finding new and more efficient ways of treating cholera -- a potential gamechanger for dozens of countries around the world.
Read more in-depth about the research by clicking or tapping here.
The Detroit Mercy research team was funded, in part, through the School of Dentistry’s faculty research grant program and includes ReBUILDetroit scholar Nour El Yaman, associate professor Joshua Thomson and senior research laboratory technician Sarah Plecha.