A new "predator" of bacteria revealed! "Five Blades that Steal Lipids" - The shocking "super weapon" PopA hidden by predatory bacteria

1. Introduction: The Strange Ecosystem of "Bacteria that Eat Bacteria"

Antibiotic-resistant superbugs (AMR) are a "silent pandemic" that the World Health Organization (WHO) is currently warning about. One of the countermeasures gaining attention is bacteria that prey on other bacteria—for example, Bdellovibrio bacteriovorus (hereafter referred to as Bdellovibrio).

Bdellovibrio rushes at its prey, Gram-negative bacteria, breaks through the cell wall, invades the interior, absorbs nutrients, divides, and then destroys the host to burst out. It is truly the wolf of the bacterial world. Research has continued since the 1970s, but its attack mechanism still contains many black boxes.en.wikipedia.org

In July 2025, an international research group centered at the University of Birmingham in the UK announced that they had elucidated part of the "weapon" of this predator. They focused on an outer membrane protein (OMP) named PopA. It was discovered that the OMP, previously thought to form monomers or trimers, actually forms a **pentamer**, capturing surrounding lipids in a unique structure that "scoops up" its surroundings.

The research team combined X-ray crystallography, cryo-electron microscopy, and AI structure prediction to visualize the "bowl-shaped" three-dimensional structure of PopA and its lipid-trapping mechanism. Furthermore, homology searches revealed that "brother proteins" that form various oligomers such as tetramers, hexamers, and nonamers are lurking in a wide variety of bacteria, highlighting the existence of an unexplored "superfamily."phys.orgnature.com

2. Details of the Research: A New Predatory Strategy of Lipid Seizure

2-1 Clash with Pre-existing Notions

Until now, the oligomerization of OMPs was linked to limited functions such as the stabilization of transport channels and the formation of extracellular protrusions (pyrops). However, PopA adopts a completely different strategy called "lipid trap." It directly captures phospholipids and fatty acids that constitute membranes, potentially causing localized defects in the host membrane and increasing lethality. Furthermore, when artificially expressed in E. coli, the host membrane partially collapsed, leading to growth defects.phys.org

2-2 Expansion of the Superfamily

AI-based FoldSeek searches detected PopA-like proteins in various environments, including marine, soil, and host-symbiotic types. This overturns the conventional image of a "weapon exclusive to predators" and suggests the possibility of a universal tool for bacterial competition. It holds potential for understanding mechanisms by which pathogens destroy host cell membranes and for applications as biofilm disruptors.eurekalert.org

3. Expert Comments

• Professor Andrew Lovering (University of Birmingham, Structural Biology)

  "This discovery rewrites the 'textbook model' of bacterial outer membranes. The pentamer structure of PopA might not be an 'exception' but a 'precedent.'"

• Professor R. Elizabeth Sockett (University of Nottingham, Microbiology)

  "Research on Bdellovibrio is shifting from unraveling predation phenomena to antimicrobial technology. The identification of the PopA superfamily serves as a bridge to this transition."

4. Reactions on Social Media

After the research announcement, hashtags like #PopA #BacterialPredator surged on X (formerly Twitter) and Mastodon.

While bioinformatics influencers praise it as a "natural antibiotic factory," synthetic biologists express caution, warning that "malfunctions could also target beneficial bacteria," leading to widespread debate.

5. Potential Medical and Industrial Applications

• Alternative Antibiotics
  Peptides/small molecule compounds mimicking PopA's lipid trap activity could establish a new class of outer membrane-disrupting antimicrobials.

• Bioremediation
  There is a concept to design artificial microbial consortia that assist in decontamination by utilizing the ability to capture lipids in oil-polluted environments.

• Synthetic Biology Platform
  The PopA superfamily could be modularized for targeting extracellular vesicles or controlling the opening of liposome-type drug delivery systems.

6. Challenges and Prospects

1. Function in Non-Predatory Bacteria
   The reason for the presence of PopA homologs in diverse bacteria remains unexplained. A reverse scenario as a membrane modification tool for the defense side (prey side) is also emerging.

2. Significance of Structural Diversity
   Do tetramers or nonamers capture larger lipid pools than pentamers, or do they target entirely different substrates?

3. In Vivo Verification
   Safety and efficacy evaluations in animal models are essential. Particularly, the impact on the gut microbiota requires both complex system simulations and experiments.

7. Conclusion

The discovery of PopA has significantly shifted the gear of predatory bacteria research from "ecological elucidation" to "utilization of molecular weapons." Peering into the "arms race among bacteria" might be the shortest route for humanity to acquire new antimicrobial strategies. The rush of discoveries of "hidden superfamilies" brought about by next-generation sequencers and AI structure prediction will likely continue.