Abstract: The present disclosure relates to a method of diagnosing Lyme disease in a subject comprising measuring the level of B. burgdorferi peptidoglycan or the level of an antibody that specifically binds to B. burgdorferi peptidoglycan (“anti-peptidoglycan agent”). The present disclosure also relates to a method of treating a Lyme disease in a subject in need thereof comprising administering to the subject an antagonist against B. burgdorferi peptidoglycan (e.g., an anti-peptidoglycan antibody or a peptidoglycan-specific hydrolase). Antagonists (e.g., anti-peptidoglycan antibodies) suitable for the present methods are also disclosed.