title: The diagnostic targeting of a carbohydrate virulence factor from M.Tuberculosis.
abstract: The current clinical management of TB is complicated by the lack of suitable diagnostic tests that can be employed in infrastructure and resource poor regions. The mannose-capped form of lipoarabinomannan (ManLAM) is unique to the surface envelope of slow-growing, pathogenic mycobacteria such as M.tuberculosis (M.tb) and facilitates passive invasion of mononuclear phagocytes. The detection of this virulence factor in urine, sputum and serum has engendered interest in its employment as a biomarker for M.tb infection. In this study, we utilize a subtractive screening methodology to engineer the first high affinity recombinant antibody (My2F12) with exquisite specificity for the α1-2 mannose linkages enriched in ManLAM from M.tb. My2F12 binds to pathogenic mycobacterial species but not fast growing non-pathogenic species. Testing on matched urine and serum samples from TB patients indicates that My2F12 works in patient cohorts missed by other diagnostic methodologies.
authors.affiliation: 1] Department of Microbiology, National University of Singapore [2] Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
authors.forename: Conrad E
authors.initials: CE
authors.lastname: Chan
authors.affiliation: 1] Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Germany [2] Department of Chemistry and Biochemistry, Freie Universität Berlin.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Götze
authors.affiliation: Department of Microbiology, National University of Singapore.
authors.forename: Geok T
authors.initials: GT
authors.lastname: Seah
authors.affiliation: 1] Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Germany [2] Department of Chemistry and Biochemistry, Freie Universität Berlin.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.affiliation: National Centre for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Nestan
authors.initials: N
authors.lastname: Tukvadze
authors.affiliation: Department of Biochemistry, National University of Singapore.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.affiliation: Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.affiliation: 1] Department of Microbiology, National University of Singapore [2] Immunology Programme, Centre for Life Sciences, National University of Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
mesh_terms: D000906:Antibodies / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000652:urine; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology* / Q000652:urine; D008562:Membrane Glycoproteins / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D019151:Peptide Library; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000906:Antibodies; D015415:Biomarkers; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019151:Peptide Library; D037521:Virulence Factors; C050016:lipoarabinomannan