Lund Receives SEK 36 Million to Uncover How Bacteria Detect and Defeat Phages
Lund University has received SEK 36 million over five years for a major research programme investigating one of the central questions in bacteriophage biology: how bacteria recognize that a virus is attacking them and activate defence mechanisms at their cell membrane. Led by Professor Vasili Hauryliuk, the project, titled “Enemy at the gates: how bacteria sense and defeat viral infection at their membrane,” will examine the earliest molecular events that allow bacterial cells to detect phage infection and prevent viral replication.
The award was announced on October 13, 2026 by Lund University and the Knut and Alice Wallenberg Foundation. The distinction between the project funding and the broader university award is important: SEK 149 million was awarded collectively to five Lund research projects, while Hauryliuk’s phage programme received SEK 36 million of that total. Across Sweden, the foundation awarded SEK 900 million to 30 projects selected following international scientific evaluation.
The project addresses a major obstacle in both fundamental phage biology and therapeutic development. A bacteriophage does not simply need to recognize a bacterium and inject its genome successfully. Once infection begins, the virus encounters an increasingly complex network of bacterial antiviral systems capable of detecting different stages of its life cycle and stopping replication before progeny phages are produced.
This bacterial immunity is far more diverse than the familiar CRISPR-Cas system. Research over the past decade has uncovered a rapidly expanding catalogue of antiphage mechanisms capable of blocking adsorption, interfering with genome entry, degrading viral nucleic acids, disrupting phage replication or triggering an abortive infection in which the infected bacterium sacrifices itself to protect neighbouring cells. For phage therapy, these intracellular and membrane-associated barriers can determine whether a virus that appears compatible with a bacterial strain actually succeeds in killing it.
The new Lund project focuses specifically on infection sensing at the bacterial membrane. This is a strategically important stage because the membrane represents one of the first interfaces between a phage and its host. Viral adsorption, genome injection and early infection can alter membrane-associated structures, ion gradients and protein complexes, creating molecular signals that bacterial defence systems may exploit to recognize invasion.
Some recently characterized antiphage systems already demonstrate how sophisticated membrane-associated immunity can become. Zorya, for example, contains a large membrane complex structurally related to ion-driven rotary motors. Other defence systems include membrane proteins that block phage genome entry, form pores or connect detection of infection to intracellular nucleases and metabolic responses. The diversity of these mechanisms suggests that bacterial membranes are not merely passive barriers against viruses but active surveillance platforms capable of detecting infection and coordinating downstream defence.
The precise scientific programme for “Enemy at the gates” has not yet been described publicly in enough detail to assign individual molecular targets to the project, so it would be premature to claim that Hauryliuk’s group will specifically study any one named defence system. The central objective announced by Lund is broader: determine how bacterial antiviral defences sense viral infection at the membrane and understand the mechanisms through which they defeat phages.
This new programme builds on several years of work by Hauryliuk and collaborators on bacterial antiphage immunity. Beginning in 2020, Hauryliuk and Professor Gemma Atkinson developed a research programme focused particularly on toxin–antitoxin-based defence systems, supported by an earlier Knut and Alice Wallenberg Foundation project. According to Hauryliuk, that funding enabled the researchers to move their activities from Umeå to Lund, establish the necessary laboratory infrastructure and develop the methods and expertise that now support the new five-year project.
One important result from this earlier programme came from research into toxin–antitoxin–chaperone systems, or TACs. These systems contain a toxin capable of inhibiting essential bacterial processes, an antitoxin that normally suppresses the toxin, and a molecular chaperone that stabilizes the antitoxin. Research led by Hauryliuk, Atkinson and an international team showed in 2024 that this architecture can be transformed into a phage detection mechanism.
In the HigBAC system studied by the researchers, a chaperone recognizes the major tail protein gpV of bacteriophage lambda. Under normal conditions, the chaperone helps maintain the antitoxin that keeps the bacterial toxin inactive. During infection, however, the viral protein competes for interaction with the chaperone, destabilizing this regulatory balance and triggering toxin activity. Instead of directly destroying the incoming phage, the bacterium responds by inhibiting its own growth and cellular activity strongly enough to prevent efficient viral propagation.
The same study characterized another TAC defence system, CmdTAC, in which activation of an ADP-ribosyltransferase toxin modifies bacterial messenger RNA and inhibits protein synthesis. Because phages depend on the bacterial translational machinery to manufacture viral proteins, shutting down translation prevents the virus from completing its replication cycle. The researchers also demonstrated the modular nature of these systems by experimentally combining a phage-sensing component from one TAC system with the toxin module of another.
These results established an important principle that extends beyond toxin–antitoxin systems: bacterial antiviral immunity can separate detection from execution. One component recognizes evidence of phage infection, while another carries out the defensive response. This modular organization creates enormous evolutionary flexibility because bacterial populations can potentially combine different sensors and effectors to recognize new viral threats.
Understanding infection sensing is particularly important because many antiphage effectors are extremely destructive. A bacterium cannot continuously activate nucleases, toxins, membrane pores or metabolic shutdown pathways without harming itself. Defence therefore needs to remain inactive under normal conditions and be triggered rapidly when phage infection begins. The molecular sensor connecting those two states is consequently one of the most important components of an antiviral system.
Recent research involving Hauryliuk has also illustrated the diversity of bacterial defence mechanisms beyond TAC systems. A 2026 Nature Microbiology study involving researchers at Harvard and Lund examined nuclease–NTPase antiphage systems and showed that related defence proteins use conserved molecular features to control bacterial immunity. Such studies are gradually revealing how defence modules remain tightly regulated until infection provides the molecular signal needed for activation.
At the same time, phages continuously evolve ways to escape these systems. A 2026 Nature Communications study involving Hauryliuk’s group showed that bacteriophage T6 can use the homing endonuclease SegB to amplify genomic regions containing anti-defence functions. One bacterial defence system examined in the study, Septu, inhibits T6 by cleaving a specific transfer RNA required for viral replication. SegB-driven amplification increases the abundance of a functional viral tRNA gene, allowing the phage to compensate for the bacterial attack.
The same mechanism could amplify other anti-defence genes targeting unrelated bacterial immune systems, demonstrating how phages can restructure their genomes to overcome several forms of immunity. These observations reinforce the evolutionary context of the new Lund project: every bacterial sensing mechanism creates selective pressure for phages capable of avoiding, suppressing or overwhelming it.
For therapeutic phages, this arms race has direct practical consequences. A bacterial strain that is susceptible to a phage according to receptor compatibility may nevertheless encode a defence system that arrests infection after genome entry. Two strains belonging to the same bacterial species can therefore differ markedly in phage susceptibility even when their surface receptors appear similar.
This partly explains why identifying a therapeutic phage can require testing large collections against individual clinical isolates. Host range is determined not only by whether a phage can attach to the bacterium, but also by whether it survives every subsequent defensive checkpoint imposed by the host.
Membrane-associated sensing could represent one of the earliest of those checkpoints. If researchers determine which molecular changes reveal phage infection to the bacterial cell, they may also identify ways in which naturally successful phages avoid detection. Comparative analysis of susceptible and resistant viruses could therefore reveal viral proteins or infection strategies capable of bypassing particular immune sensors.
Such knowledge could eventually influence phage engineering. Instead of selecting therapeutic phages solely according to their ability to bind a bacterial receptor, researchers could increasingly evaluate whether a candidate is compatible with the entire immune profile of the target pathogen. A phage blocked by a membrane-associated defence might potentially be modified, evolved or combined with anti-defence mechanisms capable of overcoming that specific barrier.
This idea remains a long-term implication rather than a result of the newly funded project. The SEK 36 million award supports fundamental research, and Lund University has not announced a therapeutic phage candidate, clinical trial or engineered product resulting from the programme. The immediate objective is to understand the biology of bacterial infection sensing rather than to produce a treatment ready for clinical development.
Nevertheless, basic discoveries in bacterial antiviral immunity have repeatedly generated applications far beyond their original context. Restriction enzymes emerged from studies of how bacteria defend themselves against phages, while CRISPR-Cas transformed from an obscure bacterial immune mechanism into one of the most important genome-engineering technologies in modern biology. Hauryliuk has similarly emphasized that bacterial immune systems represent a source of molecular tools whose capacity to recognize biological signals and trigger defined cellular responses could eventually be repurposed.
The research also connects with the broader expansion of antiphage immunity as a field. Researchers are now discovering defence systems faster than many of them can be mechanistically characterized. Genomic studies can identify genes located within bacterial defence islands and predict candidate antiviral functions, but knowing that a gene protects against phages does not necessarily explain what the system detects, when it activates or how infection is stopped.
Determining the trigger is especially difficult because phage infection is a rapidly changing process. Within minutes, the virus may attach to the bacterial surface, inject its genome, redirect transcription and translation, alter membrane properties, replicate its DNA and assemble new particles. A bacterial sensor may therefore recognize a very transient molecular event that disappears by the time traditional population-level assays are performed.
The five-year duration and scale of the Wallenberg Foundation award should allow Hauryliuk’s team to approach these questions systematically rather than studying isolated defence systems one at a time. The programme can build on Lund’s existing expertise in toxin–antitoxin biology, molecular enzymology, phage genetics and structural and biochemical characterization to connect infection sensing with downstream antiviral responses.
The project also illustrates why bacterial immunity is becoming increasingly relevant to phage therapy. As therapeutic programmes move from compassionate treatment toward standardized pharmaceutical development, researchers need more reliable ways to predict why particular phage–bacterium combinations succeed or fail. Receptor recognition, bacterial physiology and intracellular immune defence all contribute to this outcome, meaning that a useful phage must pass several layers of biological compatibility.
Hauryliuk’s project concentrates on one of those layers at its earliest point: the interface where the bacterial cell first recognizes that viral infection is underway. Understanding that recognition process could clarify why some phages are rapidly neutralized while others complete replication successfully despite encountering apparently similar bacterial hosts.
The funding also marks a continuation of Lund University’s growing research programme in phage biology and bacterial antiviral defence. The university now hosts several groups working on phage–host interactions, toxin–antitoxin systems and phage evolution, with Hauryliuk and Atkinson having developed the current programme from their earlier Wallenberg-supported collaboration.
The SEK 36 million award should therefore be interpreted as an investment in the mechanistic foundations of phage biology rather than as a new phage-therapy product announcement. The central scientific question is deceptively simple but remains incompletely answered: what exactly does a bacterial cell perceive when a phage attacks its membrane, and how does that signal become a coordinated antiviral response?
Resolving that question could reveal new defence systems, new phage countermeasures and new molecular principles governing one of the oldest evolutionary conflicts on Earth. For phage therapy, the eventual value may lie in making viral selection and engineering more predictable by understanding the immune barriers that therapeutic phages must overcome before bacterial killing can occur.
Sources :
Lund University — SEK 149 million from the Knut and Alice Wallenberg Foundation, October 13, 2026. The announcement confirms that five Lund projects received SEK 149 million collectively and that Vasili Hauryliuk’s “Enemy at the gates” project received SEK 36 million over five years.
Official Lund University announcement
Knut and Alice Wallenberg Foundation — 30 outstanding research projects awarded a total of SEK 900 million. The foundation independently lists Vasili Hauryliuk, Lund University, SEK 36 million over five years for “Enemy at the gates: how bacteria sense and defeat viral infection at their membrane.”
Knut and Alice Wallenberg Foundation — 2026 research projects
Lund University Faculty of Medicine — The war between bacteria and their virus. This article describes Hauryliuk and Gemma Atkinson’s previous work on toxin–antitoxin–chaperone antiphage systems and their relevance to understanding phage sensing.
Lund University — The war between bacteria and their virus
Mets T. et al. — Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems. Cell Host & Microbe 32, 1059–1073.e8 (2024). The study identifies phage sensing by HigBAC and characterizes CmdTAC-mediated inhibition of protein synthesis.
DOI: 10.1016/j.chom.2024.05.003
Chihara K. et al. — Phage homing endonuclease amplifies anti-defense genes to evade bacterial immunity. Nature Communications 17 (2026). The study describes SegB-mediated amplification of anti-defence genes during phage T6 infection.
DOI: 10.1038/s41467-026-71036-4
Ragucci A.E. et al. — Nuclease–NTPase antiphage defence systems use conserved molecular features to control bacterial immunity. Nature Microbiology 11, 1424–1436 (2026). PubMed
DOI: 10.1038/s41564-026-02312-8
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