One of cholera’s great enemies is found in the human gut

Wellcome Trust Sanger Institute

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Cholera-causing bacteria are locked in an evolutionary arms race with a viral nemesis, according to a new genomic study.

Experts at the Wellcome Sanger Institute, icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), the Post Graduate Institute of Medical Education & Research (PGIMER), and their collaborators, found that in the Ganges Delta, cholera bacteria rapidly gain and lose special armour that protects against attacks from the virus, known as bacteriophage ICP1.

The new research, published today (1 April) in Nature, highlighted that maintaining these anti-viral defences leads to lower disease severity of cholera in humans and reduced ability to spread outside the country for this bacterial strain.

By looking at the ecology of cholera in South Asia, this study challenges the long-held belief that the Ganges Delta is the global source of cholera. Knowing more about the strains and the factors that influence the spread of cholera bacteria in different regions could help provide an early warning system, identifying high-risk strains before they escalate and allowing for early intervention.

It could also help develop new treatments, for example, research into whether the virus could be harnessed to help stop cholera in the future.

Cholera is an acute diarrheal infection, which can be fatal within hours if untreated. It is caused by the bacterium, Vibrio cholerae (V. cholerae), which spreads through contaminated food and water1. Globally, we are in the seventh cholera pandemic, which started in 1961, with an estimated 1.3 to 4 million cases and up to 143,000 deaths per year from the condition worldwide1. It has been shown that the seventh pandemic is caused by V. cholerae strain 7PET O1, originating from the Bay of Bengal, which borders Bangladesh and India, and it was thought that the Ganges Delta was the global source of cholera.   

This new research sequenced bacterial samples from across Bangladesh and North India, creating the most comprehensive dataset of cholera in this area to date, containing over 2,300 genomes collected across approximately 20 years. They found that it was the Ganges Basin, not the Ganges Delta, that was the primary global source of cholera in that time.

By tracking the bacterial spread, they also uncovered that the bacteria do not simply follow the flow of rivers. Instead, they tend to stay within national borders, suggesting that human travel and population density are more important for cholera transmission than the natural environment.

They also found V. cholerae in Bangladesh, strain 7PET O1, rapidly gain and lose genetic elements known as defence systems, which act like armour helping them survive against their viral nemesis, the bacteriophage ICP1. Bacteriophages, also known as phages, are natural viruses that attack bacteria. They need bacteria to replicate, are generally not harmful to human cells, can rapidly kill their bacterial host, and are often found in the human gut microbiome.

By analysing cholera data in South Asia spanning 20 years, the team found evidence that the bacteria are constantly fighting off attacks from ICP1 using different armour or shields. In turn, the study shows that the ICP1 virus develops its own ‘anti-defence’ weapons to hack through those shields and continue its attack. While it has been shown previously that the presence of ICP1 in the gut is linked with less severe disease2, as the virus kills off the disease-causing bacteria2, this study shows that there is an evolutionary arms race in Bangladesh between the bacteria and ICP1, with each species developing new ways to defeat the other. This compromises the bacteria's ability to spread out of the country, limiting its ability to spread globally.

In the future, it may be possible to use our understanding of this arms race to develop new treatments or control strategies for cholera.

The study suggests that a better understanding of the natural ecology of this important disease could lead to early warning systems, highlighting V. cholerae bacteria that have lost new types of defensive shields and are more likely to cause severe disease and spread globally to cause epidemics. By identifying these high-risk strains before they spread, authorities could update treatment recommendations, deploy vaccines and improve water sanitation in specific areas to prevent local outbreaks from turning into global pandemics. Overall, by taking an ecological view of the global source of cholera, it is possible to stop the spread of these disease-causing bacteria to other parts of the world.

Dr Amber Barton, co-first author at the Wellcome Sanger Institute, said: “Our research uncovered the evolutionary struggle between cholera bacteria in Bangladesh, and the bacteriophage that preys on them. Specifically, the discovery of rapid loss and gain of V. cholerae’s protective defences and their impact on disease severity is key to understanding the factors involved in the spread of this bacterium. Without the defences, the bacteria are more dangerous to humans, and tracking this in real time, through genomics, can help us identify when the strains pose the highest risk and intervene early. Additionally, future research into cholera and microbiome interactions in other regions of the world could reveal other phages that prey on the bacteria, which may help develop new treatments in the future.”

Dr Firdausi Qadri, co-senior author at the icddr,b in Bangladesh, said: “By creating the most comprehensive genetic database of cholera bacteria samples across Bangladesh and North India, our study has shown that our understanding of the global source of cholera needs updating and refinement to consider a region that spans Bangladesh and India. We can also see that cholera spread does not follow the rivers and waterways. This suggests that, despite cholera being a water-borne pathogen, the role of human travel and population density are bigger factors in cholera transmission than the surrounding environment. Understanding this can help inform public health interventions to help stop the spread of infections.”

Professor Nick Thomson, co-senior author at the Wellcome Sanger Institute, said: “The world is in its seventh global pandemic of cholera, with the bacteria evolving and adapting to treatments and the world around it. By taking an ecological view of cholera across whole regions of the world using genomics, we have been able to dispel previous inaccuracies about the global spread of the pandemic and provide a clearer picture of the factors and threats these bacteria face. This can help inform public health strategies and future treatments to hopefully end this pandemic and protect the many thousands of people impacted.”

ENDS

Notes to Editors:

1. Cholera. World Health Organization. Available at https://www.who.int/news-room/fact-sheets/detail/cholera [accessed March 2026]
2. N. Madi, et al. (2024) 'Phage predation, disease severity, and pathogen genetic diversity in cholera patients.' Science. DOI:10.1126/science.adj3166

Publication:

A. Barton, M. H. Afrad, A. Taylor-Brown, et al. (2026) ‘Evolution of Pandemic Cholera at its Global Source’. Nature. DOI: 10.1038/s41586-026-10340-x

Funding:

This research was part-funded by the Bill and Melinda Gates Foundation and Wellcome.

Selected websites:

The Wellcome Sanger Institute

The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.

Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.

Find out more at www.sanger.ac.uk or follow us on Twitter, Instagram, Facebook, LinkedIn and on our Blog.

About Wellcome

Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health. https://wellcome.org/

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Journal

Nature

DOI

10.1038/s41586-026-10340-x 

Article Title

Evolution of Pandemic Cholera at its Global Source

Article Publication Date

1-Apr-2026

 

New antibiotic alternative fights foodborne salmonella

American Society for Microbiology

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Key Points:

• Antimicrobial-resistant Salmonella poses severe challenges to global food safety and public health.
• Biofilms formed by Salmonella on food and food-processing equipment are difficult to eliminate with conventional disinfection methods.
• Researchers have discovered an alternative method using the bacteriophage W5, which specifically targets Salmonella, paving the way for novel phage-based disinfectants.

Washington, D.C.—Researchers from China have identified a novel bacteriophage that offers a highly promising “green” biocontrol solution against foodborne Salmonella. The study was published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

This study was conducted to address the severe challenges posed by antimicrobial-resistant Salmonella to global food safety and public health. Conventional disinfection methods often fail to effectively eliminate the stubborn biofilms formed by Salmonella on food and food-processing equipment surfaces, and the overuse of antibiotics has further accelerated the emergence of drug-resistant strains. There is an urgent need to develop novel, targeted and sustainable alternative antibacterial strategies. Bacteriophages, viruses capable of specifically lysing bacteria, offer a highly promising solution.

In the new study, the researchers isolated bacteriophages that target Salmonella from wastewater and selected the most effective one, phage W5, from multiple candidates. The researchers characterized W5's morphology, stability under various conditions, growth kinetics and genomic sequence to confirm its efficacy and safety. They also evaluated W5's ability to reduce Salmonella and disrupt biofilms on foods (milk, meat, eggs) and food-contact surfaces under realistic storage conditions.

“We discovered a safe and highly effective natural virus (bacteriophage W5) that functions like a precision-guided missile, capable of eliminating harmful Salmonella on various foods and packaging materials, showing great potential as a novel guardian for food safety,” said corresponding study author and professor Huitian Gou from the College of Veterinary Medicine, Gansu Agricultural University in Lanzhou, China. “The research demonstrates that W5 can efficiently lyse planktonic bacteria and eradicate biofilms with high specificity. Genomic analysis further confirms its safety profile, as it lacks virulence and antibiotic resistance genes.”

The researchers say the findings establish a solid foundation for developing novel phage-based disinfectants or preservatives, opening an innovative pathway to combat antibiotic resistance and enhance food safety. As a natural biological entity, phage W5 offers a "green" solution for decontamination, aligning with consumer demand for clean-label products and sustainable production methods. It leaves no harmful chemical residues on food or in the environment.

“We firmly believe that phage W5 holds immense potential for seamless integration across the entire from farm to fork supply chain. It can be incorporated into multiple critical stages—for instance, as a feed additive in livestock farming, a surface disinfectant in meat processing plants, or even a preservative spray for fresh produce at the consumption end,” Gou said. “We eagerly look forward to collaborating with industry partners to translate this effective green solution from the laboratory to the market, working together to safeguard food safety.”

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of over 38,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.  

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to all audiences.

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Journal

Applied and Environmental Microbiology

 

Next generation genetics technology developed to counter the rise of antibiotic resistance

UC San Diego biologists leverage gene drive advances to stop genes responsible for drug resistance

University of California - San Diego

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image: 

Drug resistance has accelerated in recent years with the emergence of deadly bacteria and “superbugs.” UC San Diego biologists have developed a new CRISPR-based technology capable of removing antibiotic-resistant elements from populations of bacteria. 

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Credit: Bier Lab, UC San Diego

Antibiotic resistance (AR) has steadily accelerated in recent years to become a global health crisis. As deadly bacteria evolve new ways to elude drug treatments for a variety of illnesses, a growing number of “superbugs” have emerged, ramping up estimates of more than 10 million worldwide deaths per year by 2050.

Scientists are looking to recently developed technologies to address the pressing threat of antibiotic-resistant bacteria, which are known to flourish in hospital settings, sewage treatment areas, animal husbandry locations and fish farms. University of California San Diego scientists have now applied cutting-edge genetics tools to counteract antibiotic resistance.

The laboratories of UC San Diego School of Biological Sciences Professors Ethan Bier and Justin Meyer have collaborated on a novel method of removing antibiotic-resistant elements from populations of bacteria. The researchers developed a new CRISPR-based technology similar to gene drives, which are being applied in insect populations to disrupt the spread of harmful properties, such as parasites that cause malaria. The new Pro-Active Genetics (Pro-AG) tool called pPro-MobV is a second-generation technology that uses a similar approach to disable drug resistance in populations of bacteria.

“With pPro-MobV we have brought gene-drive thinking from insects to bacteria as a population engineering tool,” said Bier, a faculty member in the Department of Cell and Developmental Biology. “With this new CRISPR-based technology we can take a few cells and let them go to neutralize AR in a large target population.”

In 2019 Bier’s lab collaborated with Professor Victor Nizet’s group (UC San Diego School of Medicine) to develop the initial Pro-AG concept, in which a genetic cassette is introduced and copied between the genomes of bacteria to inactivate their antibiotic-resistant components. The cassette launches itself into an AR gene carried on plasmids, circular types of DNA that replicate within cells, thereby restoring sensitivity of the bacteria to antibiotic treatments.

Building upon this idea, Bier and his colleagues developed a follow-on system that spreads the antibiotic CRISPR cassette components via conjugal transfer, which is similar to mating in bacteria. As they described in the Nature journal npj Antimicrobials and Resistance, the researchers showed that this next-generation pPro-MobV system can exploit a naturally created bacterial mating tunnel between cells to spread the key disabling elements. They demonstrated the process working within bacterial biofilms, which are communities of microorganisms that contaminate various surfaces and can be extremely difficult to remove under conventional cleaning methods. Biofilms also contribute to the spread of disease and are created in the majority of infections that lead to serious disease, in part because biofilms help combat antibiotics by creating a protective layer of cells that is difficult for antibiotics to diffuse through. The new technology therefore carries potential in health care settings, environmental remediation and microbiome engineering.

“The biofilm context for combatting antibiotic resistance is particularly important since this is one of the most challenging forms of bacterial growth to overcome in the clinic or in enclosed environments such as aquafarm ponds and sewage treatment plants,” said Bier. “If you could reduce the spread from animals to humans you could have a significant impact on the antibiotic resistance problem since roughly half of it is estimated to come from the environment.”

The researchers also found that components of the active genetic system could be carried and delivered by bacteriophage, or phage, which are viruses that are natural evolutionary competitors of bacteria. Phage are being specially engineered to combat antibiotic resistance by evading bacterial defenses and inserting disruptive factors inside cells. pPro-MobV elements, the researchers envision, would work in conjunction with such engineered phage viruses. This active genetic platform also can incorporate a highly efficient process known as homology-based deletion as a safety measure to remove the gene cassette if desired.

“This technology is one of the few ways that I’m aware of that can actively reverse the spread of antibiotic-resistant genes, rather than just slowing or coping with their spread,” said Meyer, a professor in the Department of Ecology, Behavior and Evolution, who studies the evolutionary adaptations of bacteria and viruses.

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Journal

npj Antimicrobials and Resistance

DOI

10.1038/s44259-026-00181-z 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population

Article Publication Date

2-Feb-2026

COI Statement

Professor Ethan Bier is a co-founder of the start-up company Agragene.

Biochemistry lab at IU Bloomington finds chemical solution for tackling antibiotic resistance 

Indiana University

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image: 

After leaving the Gerdt Lab for a post-doctoral position at the Swiss Federal Technology Institute of Lausanne, Zhiyu Zang decided to focus on the human immune system. Photo courtesy Zhiyu Zang. 

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Credit: Photo courtesy Zhiyu Zang

Antimicrobial resistance — when bacteria and fungi defend themselves against the drugs design to kill them — is an urgent threat to global public health, according to the Centers for Disease Control and Prevention.

To combat this threat, the Gerdt Lab at Indiana University Bloomington studies how to weaken bacteria’s defenses against viruses.

“Bacteria get sick, too,” said J.P. Gerdt, assistant professor of chemistry in the College of Arts and Sciences at IU Bloomington. “Our lab tries to understand how their immune systems work so we can figure out how to inhibit them.” 

Bacteriophages, the viruses that attack and kill bacteria,  can be a useful alternative to antibiotics. Antibiotics kill not just pathogens but also good bacteria, but bacteriophages can be deployed in a more targeted way to kill just one problematic strain of bacteria, leaving beneficial microbes untouched.

Bacteriophages are also useful in agriculture because they provide a more targeted approach to killing bacteria. Whereas many antibiotics tend to kill not just infection- and disease-causing bacteria but good bacteria as well, bacteriophages can be deployed to kill just one strain of bacteria.

However, just as bacteria have evolved antibiotic resistance, they can also become immune to bacteriophages.

That is where the Gerdt Lab’s work comes in. Former lab member Zhiyu Zang, now a post-doctoral candidate at the Swiss Federal Technology Institute of Lausanne, discovered a chemical molecule that when paired with the bacteriophage helps the virus overwhelm a bacteria’s immune system.

This finding was revealed in Zang and Gerdt’s paper “Chemical inhibition of a bacterial immune system,” recently published in Cell Host and Microbe.

While antibiotics will likely remain the first line of defense for human bacterial infections, the Gerdt Lab’s discovery could still apply to hard-to-treat infections in humans. It could also be applied in places like agriculture, where antibiotic overuse can worsen the spread of antibiotic resistance.

A needle in a haystack

Just as millions of bacteria strains exist, there are potentially as many chemical molecules that could be deployed to inhibit bacterial immune systems. Gerdt hopes that in 10 to 15 years, his lab will create a library of inhibitors for different bacteria.

Gerdt and Zang’s strategy with this paper was to begin research with a bacterium that was relatively easy and safe for undergraduates to study. Students like Olivia Duncan, who was an undergraduate when she worked in Gerdt’s lab, helped Zang and Gerdt find molecules that chemically inhibited that bacterium’s immune system.

“Our study is important not just because we found the first example of a small molecule that can inhibit a bacteria’s immune system,” Zang said. “It’s also important because the immune system we’re studying in this paper is present in around 2,000 different bacteria species.”

This finding allows them to develop general rules and tools for a targeted approach to pathogenic bacteria with similar immune systems like  Pseudomonas aeruginosa or Staphylococcus aureus, both often resistant to antibiotics and the cause of many deadly hospital-acquired infections.

Duncan, who is the second author on the paper and currently a Ph.D. student at Cornell University, worked with Zang to identify a chemical molecule that helped a virus evade the bacterium’s immune system.

“Our goal is to have a collection of inhibitors that will work for different immune systems,” Gerdt said. “We hope that this paper will be a catalyst for other labs to work on this with us as a community. That’s what makes this paper so exciting: We’re starting something new and seeing where it takes off.”

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Journal

Cell Host & Microbe

DOI

10.1016/j.chom.2026.01.003 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Chemical inhibition of a bacterial immune system

Article Publication Date

30-Jan-2026