Biology subjects

Larrieux, N.

Publications and source records attributed to Larrieux, N..

4 recordsLinked to original sources

bioRxiv2026

Core-sheath coupling controls flagellar curvature and motility in Leptospira

Spirochete pathogens are among the most invasive bacteria known, causing syphilis, Lyme disease, and leptospirosis. Their tissue penetration depends on periplasmic flagellar filaments that, unlike other bacterial flagella, are encased in a spirochete-specific multi-protein sheath and deform the cell body into motile waves. How these filaments achieve the mechanical properties needed for invasive motility has remained unclear. Here we determine complete atomic structures of the Leptospira endoflagellar filament, revealing an elaborate sheath of 9 to 12 distinct asymmetrically arranged proteins. We show that the flagellin variant forming the filament core determines sheath composition, producing curvatures ranging from [~]3.5 {micro}m-1 to [~]5 {micro}m-1. The lower-curvature architecture, employed by pathogenic Leptospira interrogans, proves essential for motility in viscous environments and during infection. Thus, Leptospira achieves environment-specific motility through modular core-sheath coupling, linking atomic-scale structural plasticity to large-scale changes in swimming behaviour. Conservation of key sheath components suggests this mechanism may extend across spirochetes.

microbiology↗

bioRxiv2026

Bacterial targeting of host paraspeckles uncovers a new SFPQ-based regulation

Nuclear functions are key in protecting cells against infections, yet intracellular pathogens like Legionella pneumophila can exploit these mechanisms to survive. We characterized a L. pneumophila protein, LpDot1, which shares sequence similarity with the eukaryotic catalytic domain of the histone methyltransferase DOT1. Structure determination, together with biochemical and biophysical analyses, revealed that LpDot1 methylates non-histone nuclear proteins, notably the splicing factor proline-glutamine rich protein (SFPQ). Importantly, LpDot1 targets the previously uncharacterized K518, located on an important structural motif of SFPQ, therefore impairing its dimerization in vitro. During infection, L. pneumophila modulates SFPQ abundance and activities in a LpDot1-dependent manner, thereby hijacking paraspeckle organization and the host cell splicing machinery, leading to alternative splice variants of infection related genes such as NF-kB2 and CD45. To our knowledge, this is the first report of a bacterial effector directly modifying paraspeckle dynamics, providing new insight into previously uncharacterized eukaryotic regulatory pathways.

microbiology↗

bioRxiv2025

Engineering directional phosphoryl flow enables programmable signaling dynamics in bacteria

Cells must make critical decisions by integrating information from a constantly changing environment to ensure their survival. They rely on intricate signaling networks to detect external and internal cues to trigger specific responses, yet these systems are generally viewed as components wired with simpler linear connections. Bacterial phosphorelay systems offer a versatile framework for studying more complex connections and engineering new biological circuits. Here, using the well-studied Bacillus subtilis sporulation phosphorelay, we demonstrate that the directionality of information flow can be reprogrammed to generate different dynamic responses. We show that phosphoryl-transfer reversibility is an evolvable trait encoded in conserved, surface-exposed motifs of two-component system proteins. Unidirectional phosphoryl-transfer generates a short-term information storage mechanism, enabling signal integration over time and allowing phosphatases, acting at different levels, to produce different outcomes. In contrast, a bidirectional system enhanced the action of phosphatase activity early in the pathway. The ability to control phosphoryl-transfer equilibria opens exciting avenues for designing sophisticated synthetic signaling systems with enhanced decision-making capabilities.

systems biology↗

bioRxiv2020

Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel, inducing DNA-dissociation via a transmission spine

Mycobacterium tuberculosis is a pathogen with a unique cell envelope including very long fatty acids, implicated in bacterial resistance and host immune modulation. FasR is a two-domain transcriptional activator that belongs to the TetR family of regulators, and plays a central role in mycobacterial long-chain fatty acyl-CoA sensing and lipid biosynthesis regulation. We now disclose crystal structures of M. tuberculosis FasR in complex with acyl effector ligands and with DNA, uncovering its sensory and switching mechanisms. A long tunnel traverses the entire effector-binding domain, enabling long fatty acyl effectors to bind. Only when the tunnel is entirely occupied, the protein dimer adopts a rigid configuration, with its DNA-binding domains in an open state that leads to DNA dissociation. Structure-guided point-mutations further support this effector-dependent mechanism. The protein-folding hydrophobic core, connecting the two domains, is completed by the effector ligand into a continuous spine, explaining the allosteric flexible-to-ordered transition. The transmission spine is conserved in all TetR-like transcription factors, offering new opportunities for anti-tuberculosis drug discovery.

microbiology↗