Investigation into peptidoglycan biosynthetic enzymes from the Lyme disease spirochete Borrelia burgdorferi

Abstract

B. burgdorferi, the causative agent of Lyme disease, has unique chemical characteristics within its peptidoglycan (PG), such as the incorporation of L-Ornithine. This unusual structural feature may be implicated in immune evasion and may contribute to chronic symptoms such as Lyme arthritis and Post-Treatment Lyme Disease Syndrome (PTLDS). This dissertation explores the enzymes involved in PG biosynthesis in B. burgdorferi, focusing on Mur ligases, which are key to constructing the peptide stem of PG. An in vitro assay was developed to characterize MurE activity, leading to the discovery that BB0201 encodes a functional MurE ligase that exhibits activity with both L- and D-Ornithine, facilitated by a unique catalytic motif. This method was also used to study another putative Mur ligase, BB0585, to confirm its identity as a MurD ligase. These findings advance our understanding of cell wall biosynthesis in B. burgdorferi and highlight Mur ligases as potential targets for therapeutic intervention against Lyme disease.