Genetic code of cholera strain mapped to discover why it's so deadly

Disease is evolving in ways that makes it more severe and harder to control

A worker disinfects a rural isolation centre where patients are being treated for cholera in Wad Al Hilu, in Sudan's eastern Kassala state. AFP

Scientists have mapped the genetic code of a strain of cholera responsible for a devastating increase in cases in 2022, in a breakthrough hailed as a major step forward in the fight against the disease.

The research combined machine learning, genomics, genome-scale metabolic modelling and 3D structural analysis to explain why vibrio cholera is evolving in ways that makes the diarrheal disease more severe and harder to control.

Researchers in Britain and Bangladesh analysed bacterial samples from cholera patients across six Bangladeshi regions, collected between 2015 and 2021, identifying a set of unique genes and mutations present in the 2022 outbreak, when global cases more than doubled to 472,697, according to figures from the World Health Organisation.

These genetic traits are linked to the bacteria’s ability to cause severe symptoms like prolonged diarrhoea, intense abdominal pain, vomiting and dehydration, which can lead to death in severe cases.

There are between 1.3 million and 4 million cases of cholera each year worldwide. The disease can kill in hours if untreated. About one in five people experiences severe symptoms, which require rapid treatment with intravenous fluids and antibiotics. In Bangladesh, where the research was conducted, cholera is a persistent danger, with more than 100,000 cases and 4,500 deaths a year.

“By identifying the key genetic factors that drive both the transmission and severity of cholera, we've taken a significant step towards developing more effective treatments and targeted interventions,” said Tania Dottorini from the University of Nottingham. “This could save thousands of lives, not just in Bangladesh, but globally.”

The study showed that some of these disease-causing traits overlap with those that help the bacteria spread more easily, demonstrating how genetic factors enable Vibrio cholerae to survive in the human intestine, making it more resilient to environmental stress and more efficient at causing disease. Researchers said the findings also highlight the complex interactions between the bacteria's genetic make-up and its ability to cause severe illness.

By identifying genetic factors that make Vibrio cholerae more dangerous, scientists can develop better treatments and more targeted strategies to control and prevent future outbreaks. “Our findings open the door to a new era of cholera research, where we can develop tools to predict and potentially prevent severe outbreaks before they occur,” said Dr Dottorini. “The ultimate goal is to translate these insights into real-world solutions that protect vulnerable populations."

The study, which was carried out in collaboration with Bangladesh’s Institute of Epidemiology, Disease Control and Research, the International Centre for Diarrhoeal Disease Research and North South University, was published in Nature Communications.

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Vibrio cholera, the bacteria that causes cholera, usually lives in warm, salty waters, like estuaries and coastal areas. There are hundreds of strains, with only two serotypes known to cause outbreaks and epidemics.

It is not known when the first cholera outbreak occurred, but one of the first detailed written accounts described a large crop of cases in 1543 in the Ganges Delta, which killed victims within eight hours of developing symptoms. Locals struggled to bury all the dead due to the high fatality rate, according to reports.

The first cholera pandemic also emerged in the Ganges Delta in 1817, from contaminated rice. There have since been six other pandemics. The seventh originated in Indonesia in 1961 and still continues, affecting mainly less developed nations.