Abstract
During the past 30 years, notable advances have been made in understanding the etiologic agent, Borrelia
burgdorferi (Bb), and the illness that it causes. While ~30,000 cases are reported to the CDC each year, the
overall number of Bb-infected patients in the US is estimated to approach 400,000, suggesting that Lyme
disease is becoming an epidemic. Signs and symptoms of infection range in severity and most patients recover
fully after antimicrobial treatment; however, chronic serious illness and even deaths can still occur. Lyme
disease is usually diagnosed by clinical observation of erythema migrans, however, some patients do not
develop erythema migrans. Why certain patients have no accompanying symptoms at time of presentation
whereas others have numerous symptoms has not been elucidated. Many studies have been published
detailing progress in expanding the knowledge base on the microbiology of Bb and on the ecology and
epidemiology, pathogenesis and clinical aspects but laboratory based diagnosis of Lyme disease is severely
lagging behind.
It is been estimated that more than 2.7 million serum samples are tested each year for the presence of Borrelia
burgdorferi-specific antibodies in the United States alone. To meet the demand for laboratory-based diagnosis,
various new tests for direct detection of the etiologic agent, or for detection of post-infection specific antibodies
by using whole-cell lysates, recombinant antigens, or peptide antigens in enzyme immunoassays (EIA), have
been introduced into the clinical laboratory. However, the currently available Lyme disease diagnostics do not
meet the specifications for an ideal test, which would be rapid, sensitive, specific, and point-of-care. Currently,
the two step FDA approved diagnostic test will only detect the post-infection immune response to Lyme
disease pathogen, Bb, but with limited sensitivity and specificity. An ideal Lyme disease diagnostic is a test that
is specific for Bb, simple, non-invasive and relies only on readily available samples such as blood or urine. Our
proposal will provide specific targets detectable in blood at the earliest time point upon Bb infection. To develop
these tests, we will develop a comprehensive quantitative pathogen surfaceome and targeted quantitative Bb
protein remnant detection in complex host proteome backgrounds for early Lyme disease detection. We will
organize all our data into a publically accessible “Borrelia PeptideAtlas and Borrelia SRMAtlas” to provide an
ongoing resource for Lyme researchers. This proposal will have great impact and contribution to reduce
disproportionate identification of Lyme disease through the establishment of novel biomarkers that can stratify
patients. The outcome of this project is the identification and verification of highly specific and highly sensitive
pathogen targets for development into simple diagnostic assays for early stage Lyme disease patients.