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

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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biochemistry

Department dc:contributor.department

Biochemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2025

Author dc:creator

• Hart, Brittany

Chair dc:contributor.committeechair

• Jutras, Brandon L.

Committee members dc:contributor.committeemember

• Melville, Stephen B.
• Allen, Kylie Dawn
• Sobrado, Pablo

• Peptidoglycan
• Lyme Disease
• Mur Ligases
• MurE
• MurD
• Borrelia burgdorferi

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:43995

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/134943