Genetic Factors Linked to Severe Cholera Symptoms Discovered

The genetic components that make the cholera-causing bacterium so lethal have been identified by experts using a state-of-the-art computational method, and this information may be crucial to averting the terrible illness.

The International Centre for Diarrhoeal Disease Research, Bangladesh, North South University, Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), and Professor Tania Dottorini of the University of Nottingham led the ground-breaking study that was published in Nature Communications.

This groundbreaking study uses a combination of genomics, machine learning, genome-scale metabolic modeling (GSMM), and 3D structural analysis to fully understand the genetic makeup of Vibrio cholerae, the bacterium that causes cholera.

A devastating diarrheal illness, cholera poses a threat to millions of people globally, with up to 4 million cases and 143,000 deaths annually. Approximately 66 million people are at risk of contracting cholera in Bangladesh alone, where the disease causes over 100,000 cases and 4,500 fatalities yearly.

Scientists have been unable to identify the precise genetic mechanisms behind Vibrio cholerae’s evolution, which is making the disease more severe and difficult to treat. Even little is known about the genetic characteristics of these lineages that contribute to the severity of cholera. Due to a combination of symptoms, approximately 1 in 5 cholera patients will develop a severe illness (mainly diarrhea, vomiting, and dehydration).

The UK-Bangladeshi research team examined bacterial samples from cholera patients in six different districts of Bangladesh that were gathered between 2015 and 2021 for this new study. They discovered a distinct gene set and alterations in the most recent and prevalent strain of Vibrio cholerae, which is accountable for the catastrophic outbreak that occurred in 2022. These genetic characteristics are connected to the bacteria’s capacity to produce serious symptoms, which in extreme situations can be fatal. These symptoms include protracted diarrhea, excruciating stomach pain, vomiting, and dehydration.

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

The study’s conclusions also showed that several of these characteristics that cause sickness also aid in the bacteria’s easier dissemination. The results demonstrate how these genetic characteristics allow Vibrio cholerae to thrive in the human gut, increasing its resistance to environmental stress and increasing its capacity to cause illness. This study emphasizes the intricate relationships that exist between the genetic composition of the bacteria and its capacity to cause serious disease.

In the battle against cholera, this new computational framework represents a significant advancement. Scientists can create more effective treatments and focused control and prevention plans for Vibrio cholerae outbreaks by pinpointing the major genetic elements that contribute to the pathogen’s increased threat. This discovery gives fresh promise for enhancing Bangladesh’s public health and maybe saving countless lives globally.

Dr Dottorini adds: “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. The ultimate goal is to translate these insights into real-world solutions that protect vulnerable populations.

“This breakthrough was only possible through the close collaboration between our UK and Bangladeshi partners. Together, we’ve combined cutting-edge computational tools with local expertise to tackle one of the most pressing public health challenges.”

For more information: Core and accessory genomic traits of Vibrio cholerae O1 drive lineage transmission and disease severity, Nature Communications,  https://doi.org/10.1038/s41467-024-52238-0