Date
15
Sep 2023
Heure
12:30:00
Adresse
Bâtiment: Centre François Jacob Salle: Auditorium F. Jacob
Localisation
2023-09-15 12:30:00
2023-09-15 13:30:00
Europe/Paris
Microbiology departement seminar : Brandon Jutras (Virginia Tech, Blacksburg, USA) ; Friday, September 15th @11.30am ; Auditorium F.Jacob
Microbiology department seminar Friday, September 15th 2023 at 11:30 am AUDITORIUM CENTRE FRANCOIS JACOB Brandon Jutras Fralin Life Sciences Institute Centre for Emerging, Zoonotic, and Arthropod-borne Diseases, Virginia Tech, Blacksburg, USA Invited by Mathieu […]
Mathieu Picardeau
mathieu.picardeau@pasteur.fr
Présentation
Microbiology department seminar
Friday, September 15th 2023 at 11:30 am
AUDITORIUM CENTRE FRANCOIS JACOB
Brandon Jutras
Fralin Life Sciences Institute Centre for Emerging, Zoonotic, and Arthropod-borne Diseases, Virginia Tech, Blacksburg, USA
Invited by Mathieu Picardeau
Using the Bacterial Cell-wall to Explore the Unusual Biology and Pathogenesis of Spirochetes
Abstract:
Like many spirochetes, Borrelia burgdorferi is a stealth bacterium and lacks classical virulence factors associated with invasive pathogens. As such, the mechanisms that underlie Lyme disease are largely unknown. One example of this quagmire is Lyme arthritis—the proliferative synovitis of one or more large joints—which can occur after extensive antibiotic therapy and in the absence of a detectable infection. We have discovered that B. burgdorferi sheds ~45% of its peptidoglycan (PG)—the essential component of the bacterial cell-wall—from inside the cell, into its environment. B. burgdorferi PG can be detected in the synovial fluid of Lyme arthritis patients’ months after oral and/or intravenous antibiotics. When injected into a mouse, B. burgdorferi PG alone is capable of causing arthritis. Virtually all bacteria have PG but, as it turns out, B. burgdorferi PG is chemically unique and unlike any previously studied. For instance, B. burgdorferi PG peptides contain Ornithine-Glycine rather than Lysine or Diaminopimelate. PG containing Ornithine has been reported in other spirochetes that do not induce arthritis and cannot, alone, explain our earlier findings. Using high-resolution LCMS methods, coupled with metabolic labeling studies and NMR, we discovered that B. burgdorferi PG contains the unprecedented trisaccharide GlcNAc-GlcNAc-MurNAc, which is released during growth. This modification to PG glycans can be partially explained by acquisition and incorporation of the tick-vector sugar chitobiose (GlcNAc-GlcNAc). Atomic force microscopy studies reveal that GlcNAc-GlcNAc-MurNAc glycan organization is a novel means to 1) increase distance between stem peptides; 2) produce more flexible PG; and 3) collectively optimize motility to withstand the torque of endoflagella. Real-time PG tracking experiments in live animals, in conjunction transcriptomics and proteomics, suggest that the highly unusual chemical features of B. burgdorferi PG contribute to exceptionally long half-life in discrete tissues in addition to an unusual immunological response. We discuss our findings in the context of bacterial cell biology, spirochete evolution, and even in the development of an acute Lyme Disease diagnostic test