Biology subjects

Trajtenberg, F.

Publications and source records attributed to Trajtenberg, F..

6 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↗

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↗

bioRxiv2023

The Leptospira HemKR two-component system regulates heme/iron homeostasis by sensing 5-aminolevulinic acid

Heme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant. Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses. HemKR is a TCS involved in the control of heme metabolism in Leptospira spirochetes. However, the signals and molecular means by which HemKR is switched on/off, are still unknown. Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. Here we show that 5-aminolevulinic acid (ALA), a committed porphyrin biosynthesis precursor, triggers the shutdown of the HemKR pathway by stimulating the phosphatase activity of HemK towards phosphorylated HemR. HemR dephosphorylation leads to differential expression of multiple genes, including of heme metabolism and transport systems. Furthermore, HemR inactivation brings about an iron-deficit tolerant phenotype, synergistically with iron-responsive signalling systems. Such tolerance could be vital during infection in pathogenic Leptospira species, which comprise a conserved HemKR TCS. In sum, HemKR responds to abundance of porphyrin metabolites by shutting down and controlling heme homeostasis, while also contributing to integrate the regulation of heme and iron metabolism in the L. biflexa spirochete model.

microbiology↗

bioRxiv2021

Molecular basis of unidirectional information transmission in two-component systems: lessons from the DesK-DesR thermosensor

Cellular signaling systems transmit information over long distances using allosteric transitions and/or post-translational modifications. In two-component systems the sensor histidine kinase and response regulator are wired through phosphoryl-transfer reactions, using either a uni- or bi-directional transmission mode, allowing to build rich regulatory networks. Using the thermosensor DesK-DesR two-component system from Bacillus subtilis and combining crystal structures, QM/MM calculations and integrative kinetic modeling, we uncover that: i) longer or shorter distances between the phosphoryl-acceptor and -donor residues can shift the phosphoryl-transfer equilibrium; ii) the phosphorylation-dependent dimerization of the regulator acts as a sequestering mechanism by preventing the interaction with the histidine kinase; and iii) the kinases intrinsic conformational equilibrium makes the phosphotransferase state unlikely in the absence of histidine phosphorylation, minimizing backwards transmission. These mechanisms allow the system to control the direction of signal transmission in a very efficient way, showcasing the key role that structure-encoded allostery plays in signaling proteins to store and transmit information.

biophysics↗

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↗

bioRxiv2019

An asymmetric sheath controls flagellar supercoiling and motility in the Leptospira spirochete

Spirochete bacteria, including important pathogens, exhibit a distinctive means of swimming via undulations of the entire cell. Motility is powered by the rotation of supercoiled endoflagella that wrap around the cell body, confined within the periplasmic space. To investigate the structural basis of flagellar supercoiling, which is critical for motility, we determined the structure of native flagellar filaments from the spirochete Leptospira by integrating high-resolution cryo-electron tomography and X-ray crystallography. We show that these filaments are coated by a highly asymmetric, multi-component sheath layer, contrasting with flagellin-only homopolymers previously observed in exoflagellated bacteria. Distinct sheath proteins localize to the filament inner and outer curvatures to define the supercoiling geometry, explaining a key functional attribute of the spirochete flagellum. One Sentence summaryThe corkscrew-like motility of Spirochete bacteria is enabled by a unique, asymmetrically constructed flagellum that wraps around the cell body within the periplasm.

biophysics↗