The cyanobacterial lectin, microvirin-N, enhances the specificity and sensitivity of lipoarabinomannan-based TB diagnostic tests
| Autor: | Leshern Karamchand, Andrew J.M. Nel, Jonathan M. Blackburn, David W. Wright, Megan van der Horst, Westley S. Bauer |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Tuberculosis Sensitivity and Specificity Biochemistry Analytical Chemistry Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Glycolipid Antigen Tuberculosis diagnosis Lectins Electrochemistry medicine Humans Environmental Chemistry 030212 general & internal medicine Spectroscopy Lipoarabinomannan biology Diagnostic Tests Routine Chemistry Lectin biology.organism_classification medicine.disease Virology 030104 developmental biology biology.protein Antibody |
| Zdroj: | The Analyst |
| ISSN: | 1364-5528 0003-2654 |
| DOI: | 10.1039/d0an01725f |
| Popis: | Tuberculosis (TB) is one of the top ten causes of death globally, despite being treatable. The eradication of TB disease requires, amongst others, diagnostic tests with high specificity and sensitivity that will work at the point of care (POC) in low-resource settings. The TB surface glycolipid antigen, mannose-capped lipoarabinomannan (ManLAM) currently serves as the only POC molecular diagnostic biomarker suitable for use in low cost immunoassays. Here, we demonstrate the high affinity and exceptional specificity of microvirin-N (MVN), a 14.3 kDa cyanobacterial lectin, toward H37Rv TB ManLAM and utilize it to develop a novel on-bead ELISA. MVN binds to ManLAM with sub-picomolar binding affinity, but does not bind to other variants of LAM expressed by non-pathogenic mycobacteria – a level of binding specificity and affinity that current commercially available anti-LAM antibodies cannot achieve. An on-bead ELISA was subsequently developed using MVN-functionalized magnetic beads which allows for the specific capture of ManLAM from human urine with a limit of detection (LOD) of 1.14 ng mL−1 and no cross-reactivity when tested with PILAM, a variant of LAM found on non-pathogenic mycobacteria. The lectin microvirin was used for the first time to selectively bind the tuberculosis biomarker ManLAM. |
| Databáze: | OpenAIRE |
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