Scientists probe antiviral molecules in bacteria that target bacteriophages

One enjoyable aspect of a stroll through the woods on a summer’s day is the fresh smell of the forest floor. However, this smell does not come from the forest itself; it is in fact a mixture of small volatile molecules which are produced among other things by bacteria in the soil called Streptomycetes. And these molecules are also relevant elsewhere: More than two thirds of antibiotics of natural origin used in medicine are produced by Streptomycetes.

The bacteria use these molecules to protect themselves against other microorganisms. And these substances are often also effective at protecting humans. In addition to the familiar antibiotics used to fight bacterial infections, the soil bacteria also produce molecules which protect against viruses – so-called bacteriophages.

One well-known molecule, which exhibits such antiviral activity is “daunorubicin”. This cell growth inhibitor molecule is used in particular in cancer therapy. In a study conducted by HHU and FZJ, and headed by Professor Dr Julia Frunzke (Institute of Microbial Interaction), researchers have demonstrated that daunorubicin effectively inhibits the successful reproduction of various bacteriophages: When a bacteriophage infects a bacterium, a mutual destruction process is triggered.

The Max Planck Institute for Terrestrial Microbiology in Marburg and the Swiss Federal Institute of Technology in Zurich were involved in the study, which was funded under the DFG Priority Programme SPP 2330. Partners from the Collaborative Research Centre CRC1535 “MibiNet”, which is coordinated by HHU, were also involved.

Infection cycle

Professor Frunzke, corresponding author of the study, which has now been published in PNAS said: “We were able to show that daunorubicin stops or delays the infection cycle at an early stage. This results in increased production of toxic viral proteins, which are normally needed in strictly regulated quantities for a successful infection. They kill the bacterial cell at this early stage, thus preventing virus replication.”

Dr Larissa Ernst, lead author and postdoc in Frunzke’s research group: “On the other hand, where further bacterial ‘defence mechanisms’ exist, the presence of daunorubicin increases their effectiveness and enables the cell to survive while preventing the viruses in the cell from reproducing.”

Professor Frunzke on further perspectives presented by the findings: “Our understanding of bacterial immune systems has changed fundamentally in recent years. Our research contributes toward gaining a better understanding of the interplay between these different defence systems. This knowledge is particularly important for the further development of effective phage therapies.

”In times of increasing resistance to antibiotics, phages offer a promising alternative for treating infections caused by multi-resistant pathogens. As such therapies are often combined with antibiotics, it is critical to understand bacterial defence mechanisms and their potential interactions with antibiotics in detail in order to develop effective therapeutic strategies.”

Original publication

Larissa Ernst, Cornelia Gätgens, Bente Rackow, Nadiia Pozhydaieva, Elyès Gaaloul, Aileen Krüger, Johannes Seiffarth, Michelle Bund, Vivien Joisten-Rosenthal, Dietrich Kohlheyer, Björn Usadel, Alexander Harms, Katharina Höfer, Julia Frunzke; DNA-intercalating antiphage molecules trigger abortive infection through ‘mutual destruction’ and synergize with bacterial immunity; PNAS 123 (23) e2602073123, 3 June 2026