The first moments of complex life recreated through science

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In a laboratory belonging to the Swiss Federal Institute of Technology Zurich, a team of researchers has just achieved the unthinkable: reconstructing and observing live one of the most enigmatic processes in the evolution of life on Earth.

For the first time ever, the formation of an endosymbiotic relationship (an intimate association between two organisms where one lives inside the other, forming a functional unit) between two single-celled organisms has been provoked and studied closely. A microscopic alliance that allowed life to emerge on our planet. For more information about this work, you can consult the team's publication, published in the journal Nature on October 2, 2024.

A bicycle pump, a microscope and a revolutionary discovery

The story of this discovery begins with a seemingly insurmountable challenge: how to introduce a bacterium into a fungal cell protected by a virtually impenetrable wall.? Faced with this obstacle, Gabriel Giger, a doctoral student at the Swiss Federal Institute of Technology in Zurich, developed a methodology that is, to say the least, original.

His team first developed a specific enzymatic cocktail to soften the cell wall, then used an atomic force microscope equipped with FluidFM technology; a high-precision tool that can manipulate and analyze samples at the nanometric scale; transformed into a microscopic syringe.

Faced with intracellular pressure that systematically expelled the cytoplasm (liquid contents of the fungal cell) during injection attempts, Giger had the idea of ​​using… a bicycle pump. Yes, you read that right. This clever solution made it possible to generate a pressure three times higher than that of automobile tires, sufficient to force the bacteria through the cell wall.

Thomas Richards, an evolutionary biologist at Oxford University, although not involved in the study, could not help but comment on this clever use of an everyday object. ” Adapting such technology to inject bacteria into a fungus is frankly impressive “.

The pact between a fungus and a bacterium

The team chose as a study model a natural association between the fungus Rhizopus microsporus and the bacterium Mycetohabitans rhizoxinica, a duo responsible for the disease rice plant wilt. This choice was not random: in nature, these two organisms have developed such a close relationship that the fungus can no longer reproduce without its bacterial partner.

The first tests with the infamous bacteria Escherichia coli (which had caused a fake scandal during the 2024 Olympics) revealed the complexity of the enterprise. These bacteria, once introduced, multiplied too quickly, triggering a fatal immune response from the fungus.

In contrast, M. rhizoxinica has demonstrated a remarkable ability to find the right balance. It reproduced at a rate compatible with its host, avoiding the activation of immune defenses while maintaining a viable population. The “good” bacteria (Mycetohabitans rhizoxinica in this case) therefore knows how to live with the fungus without killing it, unlike E. coli.

The researchers even managed to observe how the bacteria gradually colonized the fungal spores, ensuring their transmission to subsequent generations. This ability to integrate into the host's reproductive cycle is a fundamental step in establishing a sustainable endosymbiotic relationship.

This type of relationship has played an absolutely indispensable rolein the development of life on Earth, and at several levels. Eukaryotic cells, which make up all multicellular organisms (animals, plants, and fungi), are thought to have arisen through endosymbiosis. Bacteria were engulfed by other cells, establishing a symbiotic relationship. Over time, these bacteria transformed into essential cellular organelles: mitochondria (for cellular respiration) and chloroplasts (for photosynthesis).

The acquisition of these organelles opened up new metabolic pathways, allowing organisms to exploit new ecological niches and diversify. For example, the emergence of photosynthesis through chloroplasts radically transformed the composition of the Earth's atmosphere by enriching the air with oxygen, which allowed the emergence of more complex life forms. Endosymbiosis later allowed organisms to acquire new functions, specialize, and form even more complex multicellular organisms.

Cellular symbiosis, the driving force of innovation ?

Over ten successive generations, researchers have documented excellent mutual adaptation between the two organisms. The fungus genome quickly acquired mutations that facilitated coexistence with its bacterial partner, while the bacteria optimized their integration into the fungal spores.

Julia Vorholt, a microbiologist at the Swiss Federal Institute of Technology Zurich, explains that the partners literally become “dependent on each other“. This interdependence manifests itself at both the metabolic and genetic levels, ultimately creating a new, fully functional unit.

Researchers are now considering developing synthetic cells with endosymbionts, organisms that live inside another cell with specific capabilities, that could help develop new methodological approaches in biotechnology. Potential applications could range from the design of new drugs to the targeted remediation of ecosystems. Although it has flown somewhat under the radar, this study represents a giant step in our understanding of the living world, and especially in our skills in cellular engineering.

• Swiss researchers have recreated an endosymbiotic relationship between a bacterium and a fungus, essential to the evolution of complex organisms.
• An innovative method, combining a precision microscope and a bicycle pump, made it possible to introduce the bacteria into the fungus despite a resistant cellular barrier.
• This discovery could lead to the creation of synthetic cells capable of new functions.

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