A Bicycle Pump and an Atomic Force Microscope
In 2024, Gabriel Giger, a PhD student in Julia Vorholt's microbiology lab at ETH Zurich, wired a bicycle pump to a FluidFM nanoprobe mounted on an atomic force microscope. Pressures reaching roughly three times automotive tire pressure were enough to force bacteria through the softened cell wall of the fungus *Rhizopus microsporus*.
The question being asked was ancient: how does one cell get inside another and have both survive?
Why Endosymbiosis Matters
Every eukaryotic cell contains mitochondria, descendants of an alpha-proteobacterium engulfed by an archaeon roughly two billion years ago. Plant cells carry chloroplasts descended from free-living cyanobacteria. In April 2024, Coale et al. published in *Science* the discovery of the nitroplast in the marine alga *Braarudosphaera bigelowii*, an organelle caught mid-transition from endosymbiont to true organelle.
The outcomes of endosymbiosis are familiar; the beginning has never been observed.
The Pairing
Vorholt's group chose a real-world partnership: the rice seedling blight pathogen *R. microsporus* and its bacterial partner *Mycetohabitans rhizoxinica*, whose toxin kills rice cells so both organisms can feed on the dead tissue. The fungus requires the bacterium to reproduce. Giger started with a strain cured of its natural symbiont, recreating the merger from scratch.
Fungi have rigid cell walls, so ordinary phagocytosis does not apply. After enzymatic softening, the FluidFM probe pierced the wall, but high internal turgor pressure pushed cytoplasm outward, spraying Giger with cellular fluid. The bicycle pump supplied the counter-pressure needed to drive bacteria through the wall and into the cytoplasm.
Thomas Richards of the University of Oxford described the approach as sounding like a joke but representing a significant technical advance.
E. coli Fails: Rate Must Match
With *Escherichia coli* as a control, injected bacteria replicated too quickly, depleted nutrients, attracted the fungal immune system, and were packaged for digestion within days. Reproduction-rate matching is a hard prerequisite: too fast triggers immunity.
With *M. rhizoxinica*, bacteria divided at a "just right" pace and did not trigger immune alerts.
Transmission Across Generations
Under the microscope, bacteria migrated on their own into fungal spores, the reproductive vehicles. Giger hand-picked spores and passaged the line for ten generations. Each generation showed improved bacterial survival, healthier spores, and higher efficiency.
Genome sequencing of both partners revealed that the fungal genome had also accumulated mutations to accommodate the bacteria. Adaptation runs in both directions.
Bidirectional Adaptation
The conventional model treats endosymbiosis as one-sided bacterial adjustment inside a passive host. The Zurich data show the host genome changing within ten generations to accommodate the partner. Richards called this a neglected fundamental question whose door is now open.
Failure Is the Norm
Most pairings fail. Cost-benefit mismatches, mismatched reproduction rates, and insufficient selective pressure rule out the vast majority of attempts. The relationships we observe are the surviving minority.
Toward Synthetic Endosymbiosis
The near-term application is engineered synthetic endosymbiosis: design a bacterium to perform a defined task, such as degrading pollutants or synthesizing a drug, then house it inside a plant or fungal cell so the partnership evolves together. Laila Partida Martínez of Cinvestav, who first identified the *Rhizopus*–*Mycetohabitans* relationship, framed the ceiling as imagination.
Giger, asked whether chloroplasts could be given to humans for photosynthesis, replied that mammalian cells struggle to stabilize chloroplasts, and that the energy density is far too low. The result would be green skin and the continued need for pizza.
Sources
- Giger, G., et al. *Nature* 635, 415–422 (2024). "Induction of endosymbiosis by bacterial injection into a fungal host."
- Molly Herring, Quanta Magazine, "Scientists Re-Create the Microbial Dance That Sparked Complex Life" (2025-01-02)
- Coale, T. H., et al. *Science* (2024). "Nitrogen-fixing organelle in a marine alga."
- Vilhelmiina Haavisto, ASM, "Beyond Endosymbiosis: Discovering the First Nitroplast" (2024-06-20)