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The unusual cell wall of the Lyme disease spirochaete Borrelia burgdorferi is shaped by a tick sugarAbstract Peptidoglycan—a mesh sac of glycans that are linked by peptides—is the main component of bacterial cell walls. Peptidoglycan provides structural strength, protects cells from osmotic pressure and contributes to shape. All bacterial glycans are repeating disaccharides of N- acetylglucosamine (Glc N Ac) β-(1–4)-linked to N -acetylmuramic acid (Mur N Ac). Borrelia burgdorferi , the tick-borne Lyme disease pathogen, produces glycan chains in which Mur N Ac is occasionally replaced with an unknown sugar. Nuclear magnetic resonance, liquid chromatography–mass spectroscopy and genetic analyses show that B. burgdorferi produces glycans that contain Glc N Ac–Glc N Ac. This unusual disaccharide is chitobiose, a component of its chitinous tick vector. 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. We propose that the peptidoglycan of B. 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.more » « less