Biology subjects

Le Blanc, L.

Publications and source records attributed to Le Blanc, L..

4 recordsLinked to original sources

bioRxiv2026

A structural trade-off balances mechanical resilience and supramolecular adaptability in type IV pili

Biological machines operate under mechanical load, requiring architectures that simultaneously resist force and remain functionally dynamic. Type IV pili (T4P) are bacterial filaments that experience large tensile forces during motor-driven retraction. Here, we combine cryo-electron microscopy, molecular dynamics simulations, optical tweezers, and functional analyses to define the structural basis of T4P mechanical adaptation. We determined a 2.8 [A] cryo-EM structure of the Pseudomonas aeruginosa T4P and integrated it with comparative all-atom simulations across six bacterial strains to identify a conserved force-bearing electrostatic network. Simulations predicted that this network tunes filament elasticity under load, a finding validated by single-filament force spectroscopy. Rewiring these interactions experimentally produced hyper-rigid pili that assembled normally but exhibited impaired twitching motility. Together, our findings uncover a structural trade-off between force-resistant architecture and reversible supramolecular adaptability.

biophysics↗

bioRxiv2026

Pyocyanin disrupts airway regeneration to favor chronic Pseudomonas aeruginosa infection

During chronic infections, host tissues undergo repeated cycles of injury and repair while being exposed to bacterial products. Although many virulence factors trigger immune responses, whether bacterial metabolites alter tissue architecture by disrupting regenerative programs remains largely unexplored. Here, using a primary-cell-derived human lung microtissue model, we show that the redox-active metabolite pyocyanin (PYO), produced by the opportunistic pathogen Pseudomonas aeruginosa, disrupts airway epithelial regeneration and reshapes tissue architecture, amplifying infection. PYO exposure impairs epithelial repair, leading to defects in mucociliary clearance and promoting bacterial growth. Single-cell transcriptomics and imaging reveal that PYO exposure during basal cell differentiation alters epithelial cell-type composition. Keratin-13-rich cells promote the emergence of squamous regions with defective ciliogenesis, resulting in functional defects. After characterizing how PYO remodels the epithelium, we tested how these changes impact bacterial fitness. Using transposon-insertion sequencing and live imaging of infections, we show that these regeneration defects improve the fitness of mutants that tend to form biofilms, a common feature of chronic infections. Together, our results reveal that PYO reshapes regenerative trajectories and tissue architecture in ways that subsequently alter infection outcomes, highlighting the role of secreted metabolites as potential modulators of tissue regeneration during chronic lung infections.

microbiology↗

bioRxiv2024

Bacterial growth under confinement requires transcriptional adaptation to resist metabolite-induced turgor pressure build-up

Bacterial proliferation often occurs in confined spaces, during biofilm formation, within host cells, or in specific niches during infection, creating mechanical constraints. We investigated how spatial confinement and growth-induced mechanical pressure affect bacterial physiology. Here, we found that, when proliferating in a confining microfluidic-based device with access to nutrients, Escherichia coli cells generate forces in the hundreds of kPa range. This pressure decouples growth and division, producing shorter bacteria with higher protein concentrations. This leads to cytoplasmic crowding, which ultimately arrests division and stalls protein synthesis. In this arrested state, the pressure produced by bacteria keeps increasing. A minimal theoretical model of bacterial growth predicts this novel regime of steady pressure increase in the absence of protein production, that we named overpressurization. In this regime, the Rcs pathway is activated and that abnormal shapes appear in rcs mutant populations only when they reach the overpressurized state. A uropathogenic strain of E. coli displayed the same confined growth phenotypes in vitro and requirement for Rcs in a mice model of urinary tract infection, suggesting that these pressurized regimes are relevant to understand the physiopathology of bacterial infections.

microbiology↗

bioRxiv2021

Bringing TrackMate in the era of machine-learning and deep-learning.

TrackMate is an automated tracking software used to analyze bioimages and distributed as a Fiji plugin. Here we introduce a new version of TrackMate rewritten to improve performance and usability, and integrating several popular machine and deep learning algorithms to improve versatility. We illustrate how these new components can be used to efficiently track objects from brightfield and fluorescence microscopy images across a wide range of bio-imaging experiments.

bioinformatics↗