Interaction of Amphiphilic Lipoarabinomannan with Host Carrier Lipoproteins in Tuberculosis Patients: Implications for Blood-based Diagnostics

Autor: Emmanuel Moreau, Laura M. Lilley, Basil I. Swanson, Susan E. Dorman, Shailja Jakhar, Dung M. Vu, Priya Dighe, Loreen R. Stromberg, Nicolas W. Hengartner, Harshini Mukundan, Ramamurthy Sakamuri
Rok vydání: 2020
Předmět:
Bacterial Diseases
Lipopolysaccharides
Male
Physiology
Biochemistry
Pathogenesis
Medical Conditions
Medicine and Health Sciences
Enzyme-Linked Immunoassays
Pathogen
Multidisciplinary
biology
Detectors
Lipids
Body Fluids
Actinobacteria
Infectious Diseases
Blood
Engineering and Technology
Tuberculosis Diagnosis and Management
Medicine
Biomarker (medicine)
Female
lipids (amino acids
peptides
and proteins)
Anatomy
Research Article
Adult
Tuberculosis
Lipoproteins
Science
Equipment
Research and Analysis Methods
Microbiology
Mycobacterium tuberculosis
Diagnostic Medicine
medicine
Humans
Immunoassays
Lipoarabinomannan
Bacteria
business.industry
Host (biology)
Organisms
Biology and Life Sciences
Proteins
Tropical Diseases
medicine.disease
biology.organism_classification
Biosensors
Immunologic Techniques
business
Lipoprotein
Zdroj: PLoS ONE, Vol 16, Iss 4, p e0243337 (2021)
PLoS ONE
DOI: 10.1101/2020.11.20.391037
Popis: Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.
Databáze: OpenAIRE
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