Molecular Machines
By combining molecular genetics, microscopy, and bioinformatic analysis, researchers from the CNRS Bacterial Chemistry unit, in collaboration with the Integrative and Computational Biology (BIC) platform at BIAM, have revealed a remarkably sophisticated bacterial attack system: a predatory bacterium can modulate the tip of its pili (tiny filaments on the cell surface) to better recognize and adapt to its prey. This discovery opens new perspectives in microbiology, infectious disease research, and biotechnology.
As part of their research on the molecular, cellular, and evolutionary bases of bacterial predation using Myxococcus xanthus as a model organism, scientists at the Institute of Microbiology, Bioenergies and Biotechnology (IM2B), led by Dr. Julien Herrou and Tâm Mignot (CNRS), have published findings that broaden our understanding of microbial interactions.
A unique predation strategy that adapts the weapon to the target
Some bacteria, like Myxococcus xanthus, engage in bacterial predation by directly attacking other bacteria to feed on them. This unusual lifestyle relies on direct contact between the predator and its prey. An article published this month in the journal Nature Communications presents major advances in understanding this process.
The study, led by the Bacterial Chemistry Laboratory (LCB) located at the Joseph Aiguier campus in Marseille, reveals that the molecular mechanisms behind bacterial recognition and predation are far more sophisticated than previously thought. The researchers focused on a specific type of bacterial pili—thin filaments on the cell surface—known as Tad pili. More specifically, they studied a predation-related version called « Kil system ». These filaments are locally produced precisely at the contact point between the bacterium and its prey. They consist of assemblies of numerous protein subunits called pilins.
The study’s major discovery was that the tip of the pilus can change its composition: four different complexes of “minor pilins” can assemble to form a modular tip. These interchangeable tips allow the bacterium to finely tailor its pilus according to the encountered prey, like a Swiss Army knife that adapts its tool to the task at hand.
Interestingly, the proper functioning of these tips also depends on another intracellular system known as T3SS (Type III Secretion System “needleless”). While this system is typically known for enabling pathogenic bacteria to inject proteins into host cells, it appears here to cooperate with Kil pili to facilitate predation.
Ubiquity and diversity of this strategy revealed by bioinformatics
Thanks to the expertise of the BIC platform at BIAM, this strategy was found to be far more widespread in the bacterial world than previously thought, including among some pathogens. “This opens new avenues to understand other mechanisms of cell-to-cell interaction in microbes”, note Marine Bergot and Caroline Monteil, bioinformaticians and researchers at the CEA/BIAM BIC platform.
“Analysis of several thousand complete genomes showed that structures similar to Kil pili with modular tips do exist. However, the diversity of these tips is far from fully characterized. These custom-made pili, observed in Myxococcus xanthus, could play a crucial role in interactions between pathogens and host cells or with other specific bacteria.”
If such pili were involved in the virulence of certain pathogenic bacteria, they could offer new targets for innovative treatments. By blocking these pili or their modular tips, it may be possible to disarm bacteria without killing them, thus reducing the selective pressure that drives antibiotic resistance. Alternatively, this targeting ability could be harnessed to precisely deliver antimicrobial agents to specific bacteria—like a guided antibiotic.
Dr. Julien Herrou is now continuing the functional characterization of these modular tips, known as minor pilins, in several model bacteria where this system has also been identified. “There’s still much to do following this fascinating discovery,” he emphasizes.
This breakthrough illustrates the power of integrated approaches combining molecular biology, advanced imaging, and large-scale bioinformatics to uncover the adaptive strategies of the microbial world. It opens promising paths for understanding virulence, bacterial predation, and developing targeted therapeutic tools.
References
Julien Herrou, Laetitia My, Caroline Monteil, Marine Bergot, Rikesh Jain, et al.. Tad pili with adaptable tips mediate contact-dependent killing during bacterial predation. Nature Communications, 2025, 16 (1), pp.4425. ⟨10.1038/s41467-025-58967-0⟩. ⟨hal-05086363⟩