1), we proceeded with metabolic labelling studies. As bacteria cultured with Man NAc replicated at a similar rate and reached a comparable final density to Glc NAc (Extended Data Fig. Two candidates emerged for their ability to support growth in the absence of Glc NAc: N-acetylmannosamine (Man NAc) and N-acetylgalactosamine (Gal NAc) (Extended Data Fig. By taking advantage of this auxotrophy, we reasoned that we would be able to substitute Glc NAc with other N-acetylated sugars and identify the unknown hexose. burgdorferi culture medium be supplemented with Glc NAc 11. Optimal in vitro growth thus requires that B. burgdorferi lacks many biosynthetic pathways and scavenges environmental molecules, including the peptidoglycan cell-wall precursor Glc NAc 10. The culprit responsible for this atypical alteration has remained unknown. Previous reports describe the presence of ornithine (Orn) in the peptidoglycan stem peptide 7, 9, as well as several unidentifiable components, including an unknown N-acetylated hexose (Hex NAc) linked to the Glc NAc–Mur NAc disaccharide in glycan strands 7. burgdorferi peptidoglycan, which has also been implicated in potentiating Lyme disease pathogenesis 7, 8, is thought to require unique feature(s) to counterbalance the immense flagellar stress. Motor rotation causes the flagella to torque the peptidoglycan, creating a backward wave that propels the bacterium forwards 6. Endoflagella at each pole form a ribbon that wraps around the peptidoglycan sacculus. burgdorferi pathogenesis, is the corkscrew-like motility that it uses to both escape immune cells and invade host tissues 5. burgdorferi lacks many of the classic virulence factors typically associated with invasive pathogens. Despite the public health burden posed by this ascending vector-borne disease, very little is known about what causes clinical symptoms.ī. An acute stage characterized by ‘flu-like’ symptoms is followed by a severe late stage that can involve multiple organ systems 3, 4. burgdorferi, which is an obligate parasitic bacterium, causes a biphasic infection. On transmission via the bite of an infected Ixodes scapularis tick, B. burgdorferi is estimated to cause more than 450,000 cases of Lyme disease each year, in the USA alone 2. ![]() Although alterations in peptidoglycan peptide chemistry occur across the bacterial domain, deviations from the β-(1–4)-linked Glc NAc–Mur NAc disaccharide have not previously been reported. ![]() Glycan chain lengths of six to hundreds of disaccharide repeats are terminated at the reducing-end anomeric position by a 1,6-anhydro- N-acetylmuramic acid (anhMur NAc) residue 1. Mur NAc provides a C3 lactyl moiety that anchors peptide assembly. Peptidoglycan glycans comprise a disaccharide repeat unit of N-acetylglucosamine (Glc NAc) and N-acetylmuramic acid (Mur NAc). Peptidoglycan architecture (rigid glycan strands, cross-linked by flexible peptides) is universal across bacterial taxa. The peptidoglycan sacculus protects the cytoplasmic contents of virtually all bacterial cells. burgdorferi probably evolved by adaptation to obligate parasitization of a tick vector, resulting in a biophysical cell-wall alteration to withstand the atypical torque associated with twisting motility. Mutant bacteria that are auxotrophic for chitobiose have altered morphology, reduced motility and cell envelope defects that probably result from producing peptidoglycan that is stiffer than that in wild-type bacteria. This unusual disaccharide is chitobiose, a component of its chitinous tick vector. burgdorferi produces glycans that contain Glc NAc–Glc NAc. Nuclear magnetic resonance, liquid chromatography–mass spectroscopy and genetic analyses show that B. Borrelia burgdorferi, the tick-borne Lyme disease pathogen, produces glycan chains in which Mur NAc is occasionally replaced with an unknown sugar. ![]() All bacterial glycans are repeating disaccharides of N-acetylglucosamine (Glc NAc) β-(1–4)-linked to N-acetylmuramic acid (Mur NAc). Peptidoglycan provides structural strength, protects cells from osmotic pressure and contributes to shape. Peptidoglycan-a mesh sac of glycans that are linked by peptides-is the main component of bacterial cell walls.
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