Antiviral soil compound disrupts phage infection cycle before viruses can reproduce

Bacteria also produce molecules that have an antiviral effect. Researchers from Heinrich Heine University Düsseldorf (HHU) and Jülich Research Center (FZJ) have examined the antiviral molecule daunorubicin and decoded its mode of operation against viruses in collaboration with colleagues from Marburg and Zurich. They now describe this mechanism, which primarily targets a specific group of viruses—namely bacteriophages—in the journal Proceedings of the National Academy of Sciences.

One enjoyable aspect of a stroll through the woods on a summer 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 produced, among other things, by bacteria in the soil called Streptomycetes. 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. 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 that protect against viruses—so-called bacteriophages.

One well-known molecule that exhibits such antiviral activity is daunorubicin. This cell growth inhibitor 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 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. Partners from the Collaborative Research Centre CRC1535 “MibiNet,” which is coordinated by HHU, were also involved.

Professor Frunzke, corresponding author of the study, 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, added, “On the other hand, where further bacterial ‘defense 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 said, “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 defense 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 multidrug-resistant pathogens.

“As such therapies are often combined with antibiotics, it is critical to understand bacterial defense mechanisms and their potential interactions with antibiotics in detail in order to develop effective therapeutic strategies.”

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