title: Detection of stealthy small amphiphilic biomarkers.
abstract: Pathogen-specific biomarkers are secreted in the host during infection. Many important biomarkers are not proteins but rather small molecules that cannot be directly detected by conventional methods. However, these small molecule biomarkers, such as phenolic glycolipid-I (PGL-I) of Mycobacterium leprae and Mycobactin T (MbT) of Mycobacterium tuberculosis, are critical to the pathophysiology of infection, and may be important in the development of diagnostics, vaccines, and novel therapeutic strategies. Methods for the direct detection of these biomarkers may be of significance both for the diagnosis of infectious disease, and also for the laboratory study of such molecules. Herein, we present, for the first time, a transduction approach for the direct and rapid (30min) detection of small amphiphilic biomarkers in complex samples (e.g. serum) using a single affinity reagent. To our knowledge, this is the first demonstration of an assay for the direct detection of PGL-I, and the first single-reporter assay for the detection of MbT. The assay format exploits the amphiphilic chemistry of the small molecule biomarkers, and is universally applicable to all amphiphiles. The assay is only the first step towards developing a robust system for the detection of amphiphilic biomarkers that are critical to infectious disease pathophysiology.
authors.affiliation: Chemistry Division, MS J567, Los Alamos National Laboratory, Los Alamos, NM 87544, United States.
authors.forename: Rama Murthy
authors.initials: RM
authors.lastname: Sakamuri
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Petr
authors.initials: P
authors.lastname: Capek
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Dickerson
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, Bethesda MD, United States.
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.affiliation: Chemistry Division, MS J567, Los Alamos National Laboratory, Los Alamos, NM 87544, United States. Electronic address: harshini@lanl.gov.
authors.forename: Harshini
authors.initials: H
authors.lastname: Mukundan
authors.affiliation: Chemistry Division, MS J567, Los Alamos National Laboratory, Los Alamos, NM 87544, United States. Electronic address: basil@lanl.gov.
authors.forename: Basil I
authors.initials: BI
authors.lastname: Swanson
mesh_terms: D015415:Biomarkers; D015374:Biosensing Techniques; D019084:Fluorescent Antibody Technique, Indirect; D054884:Host-Pathogen Interactions; D008024:Ligands; D013501:Surface-Active Agents; D037521:Virulence Factors
chemical_list: D015415:Biomarkers; D008024:Ligands; D013501:Surface-Active Agents; D037521:Virulence Factors
keywords: Amphiphiles; Biomarkers; Lipid bilayer; Membrane insertion assay; Mycobactin; Phenolic glycolipid