Recently, a breakthrough study led by Tania Dottorini, professor from the School of Veterinary Medicine and Science at the University of Nottingham and director of the Centre for Smart Food Research at The Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute (hereafter referred to as "the China Beacons Institute"), has been published in the prestigious journal Nature Communications. This research, conducted in collaboration with Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), International Centre for Diarrhoeal Disease Research, Bangladesh, and North South University, reveals the significant impact of genomic traits of the cholera pathogen—Vibrio cholera O1—on disease transmission and severity. This breakthrough provides vital insights into cholera outbreaks and offers new directions for global public health strategies in combating the disease.

Cholera: The Invisible Killer of Global Health

As a deadly acute intestinal infectious disease, cholera has triggered seven major pandemics worldwide since the 19th century, claiming over a hundred million lives and remaining a substantial threat to human health today. Once contracted, patients can die from dehydration within hours. Although cholera is preventable and treatable, the World Health Organisation reports that in recent years, up to 4 million cases and as many as 143,000 deaths each year. In Bangladesh alone, where cholera is a persistent danger, with over 100,000 cases and 4,500 deaths annually. “Cholera remains a significant public health challenge globally, especially in regions with weak healthcare systems,” says Professor Dottorini.

People infected with cholera always exhibit varying degrees of severity due to typical symptoms like diarrhoea, vomiting, and dehydration. This has led scientists to hypothesise that key features may be hidden within the cholera bacterium’s genome, crucial for determining the severity of the disease. However, previous research limitations have left scientists with scant knowledge about these genomic traits. Furthermore, Professor Dottorini points out a more complex issue: “These cholera bacteria are not static; they can acquire greater environmental adaptability and resistance through genetic changes, making new strains harder to control. Understanding how these genes change is vital for us.”

What genetic secrets lie behind the cholera bacterium? How might this research aid scientists in intervening against cholera?

Professor Dottorini’s study integrates cutting-edge research methods, including machine learning, genomics, genome-scale metabolic modelling (GSMM), and 3D structural analysis, to analyse bacterial samples from cholera patients across six regions in Bangladesh from 2015 to 2021. Using advanced computational tools, the team identified key genetic factors behind the cholera bacterium and revealed, for the first time, a unique set of genes and mutations between two major lineages (BD-1.2 and BD-2).

The findings indicate that, beyond gene exchange and genetic variation, the genetic mutations in cholera bacteria play a crucial role in enhancing their environmental adaptability. This not only facilitates disease transmission but also exacerbates the severity of cholera. Additionally, the research reveals a close correlation between certain pathogenic traits and the bacterium’s transmission capabilities, confirming the complex interactions between bacterial genetic composition and their potential to cause severe disease, thus ushering in a new era for cholera research.

Professor Dottorini states, “By identifying the key genetic factors that contribute to cholera transmission and severity, we have taken a significant step towards developing more effective treatments and targeted interventions. Our ultimate aim is to translate these findings into practical solutions that protect the most vulnerable populations.” She adds. “We look forward to these findings being swiftly translated into real-world medical applications to make a greater contribution to the health and wellbeing of people globally.”