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Blocking off highway to infections
How does a normally harmless fungus transform itself into a formidable pathogen? By studying morphological changes to Candida albicans, the scientists have demonstrated a surprising mechanism: increased fluidity of the cytoplasm1 may play a crucial role in infection. A discovery2 that offers new therapeutic opportunities.
Microscopic fungi
Candida albicans is one of the more than 200 Candida species currently known to scientists, and some 20 of them can affect humans. “Among these pathogenic fungi, Candida albicans is the most common cause of infection,” emphasises Robert Arkowitz, CNRS research professor at the iBV3, in Nice (southeastern France).
Naturally present in the mucous membranes of the body, Candida albicans does not generally make its presence felt. However, it can launch an opportunistic attack when its environment changes, causing superficial fungal infections that affect the mouth (thrush) or genital mucosae. The fungus can also spread through the blood and affect one or more organs, which in this case is referred to as a systemic infection.
“The mortality rate can then reach 25%, particularly in individuals whose immune system is compromised, such as patients undergoing chemotherapy, for example,” observes the microbiologist. Systemic candidiasis is usually due to hospital-acquired infections, where the fungus can follow the path of catheters or implanted medical devices.
From buds to filaments
Understanding how the yeast becomes pathogenic is crucial to combating these infections. Pathogenicity is indeed accompanied by a morphological transition. The fungus develops from an oval budding shape to an invasive filamentous form. This enables it to penetrate and more easily damage the tissues of its host, and colonise its organs.
A variety of events (rise in temperature, variations in pH, lower levels of nutrients, etc.) can trigger this morphological transition. But what happens within the fungus? Arkowitz and his colleagues looked at the intracellular reorganisation that subsequently occurs within the cytoplasm.“We focused on the cytoplasm, which is the intracellular medium that contains the organelles4, in order to try and clarify the relationship between molecular crowding and the morphological state of C. albicans. The cytoplasm can be seen as a sort of ball pool,” he explains.
This image makes it possible to visualise the problem of moving within a crowded space, such as a cytoplasm full of numerous molecules and organelles. Reducing molecular movement can have dramatic effects on the reactions in play within the cells.
The importance of fluidity
To achieve their aim, the scientists needed first of all to develop an observational technique. “No tool was available to study the C. albicans cytoplasm at a mesoscopic scale, that of major protein complexes measuring 10 to 100 nanometres,” Arkowitz points out.
The team therefore used tracers in the form of nanometric particles developed by their colleague Morgan Delarue, a CNRS research professor at the LAAS5 in Toulouse (southwestern France). They monitored the movements of these tracers in order to measure the local mechanical properties of the cytoplasm – and observed that diffusion (the ability of particles to spread) appeared to be greater in hyphae – the filamentous form – than in oval budding cells.
Lower concentrations of ribosomes
The question then was to understand what enabled this greater fluidity of the cytoplasm. The authors therefore conducted simulations which showed that simple changes to cell geometry (transition from the budding form to that of filaments) were not sufficient to explain the increase in cytoplasmic fluidity.
They henceforth suspected that the concentration of ribosomes (RNA molecules responsible for translating messenger RNA into protein) might play a role in crowding and hence cytoplasmic fluidity. “By combining several cross-disciplinary and cutting-edge techniques (fluorescence microscopy, mass spectrometry and electron cryomicroscopy), we were able to show that the longer the filament, the lower the concentration in ribosomes,” Robert Arkowitz explains.
Targeting ribosome production
To test their hypothesis, the team created a mutant yeast strain displaying a defect in ribosome genesis. “We then observed that the cytoplasm was more fluid in this mutant strain, and that this triggered filament formation!” the microbiologist enthuses.
A reduction in cytoplasmic crowding with filamentous cells thus arises from lower ribosome production. The resulting increase in fluidity then enables biochemical processes to occur more easily.
These findings offer new opportunities for combined therapy to fight C. albicans, and in particular to target ribosome biogenesis. This is all the more essential since Candida species are developing increasingly strong resistance to the antifungal drugs used to combat them.
- 1. The part of the cell located between the nucleus and the membrane, whose components perform the main cellular functions.
- 2. A. Serrano, C. Puerner, L. Chevalier, et al., “Decreased cytoplasmic crowding via inhibition of ribosome biogenesis can trigger ‘Candida albicans’ filamentous growth”, Nature Microbiology, 2026: https://doi.org/10.1038/s41564-025-02205-2
- 3. Institut de Biologie Valrose (CNRS / INSERM / Université Côte d’Azur).
- 4. Specialised components of the cell with a specific function.
- 5. Laboratoire d’Analyse et d’Architecture des Systèmes (CNRS).
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