Delivering the first complete atomic structures of spirochete endoflagella and demonstrating that flagellin identity programs curvature and virulence, this work unlocks the structural logic of invasive motility in pathogens behind syphilis, Lyme disease, and leptospirosis.
Spirochetes cause some of the most serious human infections, including leptospirosis, Lyme disease, and syphilis, and our central finding explains how the flagellum that drives their invasive motility works: in Leptospira, the flagellin isoform forming the core of the filament dictates how the surrounding multi-protein sheath assembles, and that architecture sets how curved the filament is. The filament is a flagellin core wrapped in a precisely ordered, asymmetric sheath of a dozen proteins, all confined within the periplasm between the bacterium's inner and outer membranes. Genetically swapping the core isoform modulates curvature and abolishes virulence even though the mutant still swims in aqueous media, pinpointing curvature as central to how these spirochetes propel themselves through host tissue.
Leptospira endoflagellar filaments comprise 9-12 distinct asymmetrically arranged sheath proteins whose composition is determined by core flagellin isoform identity through glycosylation-mediated coupling, producing species-specific filament curvatures (3.5-5.6 μm⁻¹) that are essential for viscosity-dependent motility and virulence in pathogenic species.
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 µm-1 to ∼5 µm-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.