Scanning electron micrograph of an Escherichia coli cell (red) infected by bacteriophages (green).
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World Antimicrobial Resistance Awareness Week: The search for new weapons against bacterial infections
Researchers at the HZI, HIRI and HIOH explore molecular mechanisms and the therapeutic potential of bacteriophages
Since the middle of the 20th century, antibiotics have been among the greatest successes in medicine. They save millions of lives every year, prevent complications during operations and make many therapies possible in the first place. But their success has a downside: More and more bacteria are developing strategies to evade the attacks of these drugs. Resistant germs are spreading around the globe, against which hardly any drugs are effective. With the annual World Antimicrobial Resistance Awareness Week (WAAW) from 18 to 24 November, the World Health Organization reminds us how important it is to use antibiotics carefully and how urgently new approaches are needed to continue fighting infections effectively in the future. Almost 20 research groups in the research topic “Novel Anti-Infectives” at the Helmholtz Centre for Infection Research (HZI) are developing new drugs against infectious diseases.
Scientists at the HZI and its sites in Würzburg and Greifswald are exploring an additional strategy against bacterial infections: they are studying the therapeutic potential of bacteriophages, or phages for short. These are viruses of microbes. They precisely recognize their host cells, inject their genetic material and replicate in them until the bacterial cell bursts and releases new phages. Phages are harmless to humans as they do not replicate in human cells. They are found in unimaginable numbers in bodies of water, in the soil and even in our intestines and replicate in the bacteria living there. They have been keeping bacterial populations in balance for many millions of years. Scientists at the HZI, the Helmholtz Institute for RNA-based Infection Research (HIRI) and the Helmholtz Institute for One Health (HIOH) are specifically investigating this ancient biological interplay in order to develop new therapies. HIRI and HIOH are sites of the HZI in cooperation with the Julius-Maximilians-Universität Würzburg (JMU) and partner institutions in Greifswald, respectively.
Bacteriophages have a huge repertoire of functions to take control of their host bacterium. “We need to move away from assessing bacteriophages and their efficacy against bacteria only under model conditions,” says Dr. Milan Gerovac, head of the junior research group “Complexes in Phage-infected Cells” in the HZI's MICROSTAR program. “An infection creates stress for the bacteria and for the phages. We also reproduce these stress conditions in our research in order investigate the function of as many factors as possible that we do not yet understand.” He is focusing on the group of jumbo phages, whose genome is made up of DNA and comprises several hundred genes.
Electron micrograph of Pseudomonas aeruginosa infected by the jumbo phage ΦKZ (red).
To better study the large genome of jumbo phages, Gerovac developed an innovative RNA technology as a postdoctoral researcher under Prof. Jörg Vogel, enabling specific intervention in phage development. This allowed the researchers to systematically switch off a wide variety of phage proteins in a jumbo phage of the hospital germ Pseudomonas aeruginosa and thus identify proteins central to its development. Vogel is Managing Director of the HIRI and heads the HIRI department “RNA Biology of Bacterial Infections”. He has high hopes for phage research: “If we succeed in harnessing the potential of phages for therapeutic purposes, this would be a promising new approach, especially in light of increasing antibiotic resistance.”
A completely different group of bacteriophages is the focus of research by Jun. Prof. Jens Hör at the HIRI: RNA phages. “Their genetic material consists of RNA, which makes them fundamentally different from DNA phages. For example, it allows RNA phages to escape the bacterial immune system CRISPR-Cas, which can recognize and cut DNA sequences,” says Hör. He heads the junior research group “Molecular Principles of RNA phages”. With a recently acquired ERC Starting Grant, he is investigating the basic mechanisms of how RNA phages efficiently control their replication, which host factors they utilize during this process and how bacteria defend themselves against the infection. “On the one hand, understanding these mechanisms is a prerequisite for the use of RNA phages as therapeutics. On the other hand, it opens up the possibility of discovering completely novel biotechnological tools,” says Hör.
Untapped resources for phage therapy
Many research teams around the world are using wastewater to search for new phages that are effective against pathogens. Dr. Jan Gogarten, head of the junior research group “Evolutionary Community Ecology” at the HIOH, however, is using a very special source in his search for new phages: the feces of non-human primates. Wild primates have a more diverse microbiome than humans, especially those with a Western lifestyle. As a result, their phage community is also more diverse. “This diversity could represent an untapped resource for phage therapy. In particular, we hope to identify phages with a broader host range that are still relevant to the bacteria that infect humans,” says Gogarten. Bacteriophages could also serve as an indicator of where contact between humans and wild animals takes place. The resulting transmission of microorganisms is also a danger for wild animals, whose populations can be endangered by human pathogens. Additionally, it poses a risk to global health as new zoonoses can emerge.
Even though bacteriophages have great therapeutic and biotechnological potential, they will not be able to solve the antimicrobial resistance crisis on their own. “The problem with bacteriophages is production. With antibiotics, once research and development are complete, we can mold the active ingredient into a product that can be manufactured millions of times over. Phage therapy is much more individual. Depending on the germ, individual phages or phage cocktails are required,” says Prof. Mark Brönstrup, head of the department “Chemical Biology" at the HZI. Bacteriophages will therefore not be able to completely replace antibiotics in the long term. However, through systematic research such as that being conducted at the HZI, they can become a complementary weapon in the arsenal against bacterial infections.
Bacteriophages, or phages for short, are viruses that infect bacteria. Using phages therapeutically could be very useful in fighting antibiotic-resistant pathogens, but the molecular interactions between phages and host bacteria are not yet sufficiently understood. Jörg Vogel's research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) and the Institute of Molecular Infection Biology (IMIB) in Würzburg has now succeeded in specifically interfering with phage reproduction using a molecular tool called antisense oligomers (ASOs). According to the researchers, this innovative RNA technology offers new insights into the molecular world of phages and is expected to advance the development of future therapeutic applications. The study has been published in the journal Nature.
In the fight against multi-resistant bacteria, bacteriophages—the natural enemies of bacteria—are attracting increasing research interest. However, the targeted therapeutic application of these “bacterial killers” requires a precise understanding of their molecular basis. This is at the heart of the research in the team of Jens Hör from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg. Starting in February 2026, the European Research Council (ERC) will fund his research project “RIBO-PHAGE” with a 1.5 million euro ERC Starting Grant for a period of five years.
Bacteriophages are viruses that specifically attack bacteria but are harmless to humans. They attach themselves to bacteria, inject their genetic material, and reprogram the cells so that they only produce phage genetic material – until they eventually burst and release new phages. In theory, phages are a promising alternative to antibiotics, but in practice, major challenges must be overcome. In this episode of the HZI podcast “InFact”, Jun. Prof. Jens Hör, head of the junior research group “Molecular Principles of RNA Phages” at the Helmholtz Institute for RNA-based Infection Research (HIRI), talks about his research on this fascinating tool in the fight against resistant germs.
![[Translate to English:] Rasterelektronenmikroskopische Aufnahme einer Escherichia coli-Zelle (rot), die von Bakteriophagen (grün) infiziert wird.](/fileadmin/_processed_/1/6/csm_Escherichia_coli_phage_c57d3dd91f.jpg)
![[Translate to English:] Elektronenmikroskopische Aufnahme von Pseudomonas aeruginosa, infiziert mit dem Jumbophagen ΦKZ (rot).](/fileadmin/_processed_/1/5/csm_09_PALo44_pHIKZ_10min_UAc_PB_14_986251b1b5.jpg)
![[Translate to English:] Charlotte Schwenner](/fileadmin/_processed_/6/9/csm_Charlotte_Schwenner_7952cfe0a7.webp "Dr Charlotte Schwenner")
