After a successful application for an ERC Starting Grant, Simona Huwiler discusses the potential of the predatory bacterium Bdellovibrio bacteriovorus to address the growing concerns of antibiotic resistance.
The impact of antimicrobial resistance on public health is concerning. A recent study by the World Health Organization (WHO) in its 2025 Global AMR Surveillance Report showed that in 2023, one in six bacterial infections worldwide had antibiotic resistance. Another study examining 2019 data reported that approximately 5 million deaths were linked to AMR. Of these, approximately 3 million deaths were directly attributable to antimicrobial resistance.
This widespread development of antimicrobial resistance makes it increasingly difficult to treat bacterial infections in hospitals, and also threatens a variety of medical procedures, such as surgery and cancer treatment.
The current goal is to prevent the inappropriate use of antibiotics, especially when they are ineffective. Many governments are working to limit the use of antibiotics of last resort in livestock production, as they are essential for the treatment of certain infectious diseases. Antibiotics are available without a prescription in some countries and are often misused for viral infections, but efforts are being made to prevent this.
Potential solution: Budellovibrio Bacteriovorus
Bdellovibrio bacteriovorsis is a “living antibiotic”, a predatory bacterium that has its own energy, is agile and can actively seek out other bacteria. It attaches to other Gram-negative bacteria on the outside and punctures the outer membrane and peptidoglycan cell wall, allowing it to enter its prey. It preys on its prey internally, divides, and new predator cells emerge from the remains of the bacterial prey. In contrast, traditional antibiotics generally work by spreading until they reach and kill the target bacteria.
This predatory bacterium primarily kills and preys on other Gram-negative bacteria. Many are included in the WHO list of bacterial priority pathogens, such as carbapenem-resistant Klebsiella pneumoniae and Escherichia coli. Understanding the mechanisms this predator uses to damage and kill its prey could lead to the development of new drugs to combat AMR.
One of the drawbacks of these “living antibiotics” is their large size compared to the small molecules that make up traditional antibiotics. This limitation may limit future applications primarily to the treatment of surface infections such as lung and intestinal wounds and mucosal surfaces. These “living antibiotics” are too bulky to penetrate deeply into tissues, so they may not be effective against infections deep in tissue, such as intracellular infections, where traditional antibiotics excel.
However, B. bacteriovorus has multiple mechanisms involved in the attachment and removal of its bacterial targets. Traditional antibiotics typically have a single mode of action to kill bacteria, making it easier for pathogens to develop resistance. In contrast, the mechanisms of “living antibiotics” are diverse, which can make it more difficult for bacteria to adapt and develop resistance.
Promising safety data
Many available studies show that B. bacteriovorus is safe and effective in eliminating many infections caused by Gram-negative pathogens. A significant amount of research has been conducted in the past and is still ongoing, demonstrating that it is effective even against bacteria that are resistant to antibiotics. This effectiveness appears to be independent of whether the bacteria carry antibiotic resistance genes.
The studies conducted include a variety of standard animal models such as mice, rats, and zebrafish. However, more sophisticated models, potentially including differentiated human cell cultures and organoids, may be required to better simulate the human condition. Studies involving human cells have been conducted to assess toxicity, and the results suggest that it is well tolerated.
Timeline for widespread application
Clinics in the Western world now commonly have rapid diagnostics in place to identify alternative antibiotics in cases of multiple antibiotic resistance. Therefore, in most cases there is no urgent need in the clinic. However, with antibiotic-resistant infections steadily increasing and Western populations aging and becoming more susceptible to infections, this may become more urgent in the future.
Non-medical products containing B. bacteriovorus are now being sold in the UK and expanding to the EU market to protect and rebuild the local microbiome. Although some trials have already been conducted, blinded and controlled trials are still needed, which is an important step towards medical approval.
An important future goal is to manufacture products using B. bacteriovorus under Good Manufacturing Practice (GMP) standards. This ensures that these predatory bacteria can be consistently produced in a safe and controlled manner, making them suitable for human medical use. With GMP-compliant products, clinical trials can be initiated to compare the results of the active treatment and the placebo group to assess efficacy.
In the future, one of the first applications of this therapy could be in situations where traditional methods fail. This type of experimental treatment or compassionate use could be given to patients dealing with multidrug-resistant strains, as long as the patient consents and the necessary framework is in place.
Another avenue to advance this potential new therapy based on B. bacteriovorus is its use in chronic infections such as cystic fibrosis, where patients require long or frequent antibiotic treatment. This approach may help reduce unpleasant side effects associated with some antibiotics. If a patient is infected with a multidrug-resistant pathogen, treatment with bacteriophage (bacterial virus) or, in some cases, B. bacteriovorus may be the last resort.
Additionally, efforts are being made to produce Budellovibrio in encapsulated form, particularly for use in agriculture and aquaculture. Budellovibrio has been proven to fight bacterial pathogens that affect shrimp and is used in shrimp aquaculture. In agriculture, it is being studied as a means of preventing diseases that affect crops such as potatoes. However, it is important to note that this method is only effective against certain bacterial plant pathogens, and many plant diseases are caused by fungi. Nevertheless, bacterial plant pathogens pose a significant concern in human medicine.
Remaining questions and barriers
The main future research focus will be on differentiated human cell and organoid models, which will bring us closer to practical applications in humans. In the future, there is hope that these predatory bacteria may be engineered to target only pathogenic bacteria while leaving beneficial bacteria intact.
From an ecological perspective, major questions remain about how these predatory bacteria interact with the microbiome. Most microbiomes have very small numbers of predatory bacteria. However, we still do not understand how introducing more of them will affect the microbiome. Most antibiotics often kill a large portion of the microbiome without thinking twice. In contrast, phage therapy utilizes viruses that target specific bacteria, typically preserving the microbiome. However, selecting the appropriate phage requires accurate diagnosis.
Additionally, the challenges posed by the regulatory environment must be considered. For antibiotics, there are standard requirements and procedures for obtaining approval from bodies such as the European Medicines Agency (EMA). This process can be difficult when applying the same framework to B. bacteriovorus because B. bacteriovorus is a living organism. Fortunately, there is an opportunity to interact with the EMA regarding phage therapy, for example. If there is an unmet medical need, there may be ways around some standard regulatory procedures. It may be beneficial to study the regulatory framework for probiotics, especially since probiotics are also bacteria, and some probiotic products have recently received US Food and Drug Administration (FDA) approval. In general, it is expected that the timeline for obtaining approval for these “live antibiotics” is likely to be much longer than for standard antibiotics, based on their unique properties.
Secure funding for basic research in predatory bacteria through ERC Starting Grant project
As of November 10, 2025, the EU Program Agreement (EUPA) with Switzerland was signed in Bern, retroactively linking Switzerland and Horizon Europe. This will enable me to carry out my ERC Starting Grant 2025 project investigating the interaction of predatory and prey bacteria at a Swiss university, namely the University of Bern. Unfortunately, this was not possible with the ERC Starting Grant 2024 call. EUPA is part of the bilateral agreement III between the EU and Switzerland and, based on my view, is of great importance for Swiss science and innovation.
This article will also be published in the quarterly magazine issue 24.
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