Lyme disease (LD) is the most commonly reported vector-borne disease in the United States with approximately 38,000 confirmed and probable cases in 2009. The currently recommended method for diagnosing LD is a two-tiered serology-based test that is limited in its ability to differentiate active from previous infection, diagnose early LD, and is not standardized among laboratories. These limitations can result in misinterpretations and have led to millions of diagnostic tests (FDA approved and non-approved) being performed each year for this infection. Thus, a fresh approach for improved diagnostic development is critical to the field. Studies applying the global evaluation of small molecule biomarkers, metabolomics, for the discovery of biosignatures and biomarkers for monitoring cancers and metabolic diseases have shown tremendous promise. Although this technology has not been widely applied for infectious diseases, it is recognized that infectious diseases are manifested based on alterations to the biochemistry of a biological system. Thus, as is now being shown with other infections, we hypothesize that metabolomics offers an innovative approach for identification of biosignatures and biomarkers of LD. This R21/R33 application proposes to, in the first two years, elucidate multiple metabolome-based biosignatures of LD; initiate identification of products that comprise these biosignatures; and establish tools for the elucidation of the Borrelia burgdorferi metabolome. Successful completion of these initial studies and tool development efforts will lead to efforts in Years 3-5 to qualify the LD biosignatures; complete the molecular identification of the biosignature products; and provide a comprehensive analysis of the B. burgdorferi metabolome. These activities encompassing the entirety of the R21/R33 program are framed within three Specific Aims: 1) Develop and qualify metabolic biosignatures that differentiate active LD from look-alike infections, and define the stages of disease including cured LD; 2) Identify and validate the chemical structures of the metabolites that comprise the biosignatures of LD; and 3) Evaluate the metabolic profile of B. burgdorferi. The overall goal at the end of five years will be to have qualified LD biosignatures that can be applied in clinical laboratories using mass spectrometry or another analytical technique suitable for a multi-analyte small molecule diagnostic.

Public Health Relevance

The proposed research will identify novel small molecule diagnostic biomarkers for Lyme disease. The diagnostic marker profile will include both products of the human host and the pathogen, Borrelia burgdorferi. These will be used to develop biosignatures for improved Lyme disease diagnostic assays that are not based on classical serology and that can differentiate between the stages of Lyme disease and provide a test of cure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33AI100228-04
Application #
8867127
Study Section
Special Emphasis Panel (NSS)
Program Officer
Ilias, Maliha R
Project Start
2014-06-10
Project End
2017-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Pegalajar-Jurado, Adoracion; Fitzgerald, Bryna L; Islam, M Nurul et al. (2018) Identification of Urine Metabolites as Biomarkers of Early Lyme Disease. Sci Rep 8:12204
Molins, Claudia R; Ashton, Laura V; Wormser, Gary P et al. (2017) Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI). Sci Transl Med 9:
Molins, Claudia R; Ashton, Laura V; Wormser, Gary P et al. (2015) Development of a metabolic biosignature for detection of early Lyme disease. Clin Infect Dis 60:1767-75