The Diagnostic Targeting of a Carbohydrate Virulence Factor from M.Tuberculosis

Overview

Journal Sci Rep

Specialty Science

Date 2015 May 16

PMID 25975873

Citations 16

Authors

Conrad E Chan

Sebastian Gotze

Geok T Seah

Peter H Seeberger

Nestan Tukvadze

Markus R Wenk

Brendon J Hanson

Paul A Macary

Affiliations

Soon will be listed here.

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.

Citing Articles

KLK12 Regulates MMP-1 and MMP-9 via Bradykinin Receptors: Biomarkers for Differentiating Latent and Active Bovine Tuberculosis.

Wang Y, Qu M, Liu Y, Wang H, Dong Y, Zhou X Int J Mol Sci. 2022; 23(20).

PMID: 36293113 PMC: 9603359. DOI: 10.3390/ijms232012257.

Monoclonal antibodies to lipoarabinomannan/arabinomannan - characteristics and implications for tuberculosis research and diagnostics.

Corrigan D, Ishida E, Chatterjee D, Lowary T, Achkar J Trends Microbiol. 2022; 31(1):22-35.

PMID: 35918247 PMC: 9771891. DOI: 10.1016/j.tim.2022.07.001.

Diagnostic value of Lipoarabinomannan antigen for detecting Mycobacterium tuberculosis in adults and children with or without HIV infection.

Yin X, Ye Q, Wu K, Zeng J, Li N, Mo J J Clin Lab Anal. 2022; 36(2):e24238.

PMID: 35034374 PMC: 8842169. DOI: 10.1002/jcla.24238.

The cyanobacterial lectin, microvirin-N, enhances the specificity and sensitivity of lipoarabinomannan-based TB diagnostic tests.

van der Horst M, Karamchand L, Bauer W, Nel A, Blackburn J, Wright D Analyst. 2020; 146(4):1207-1215.

PMID: 33367346 PMC: 8374243. DOI: 10.1039/d0an01725f.

Potential Plasticity of the Mannoprotein Repertoire Associated to Virulence Unveiled by Mass Spectrometry-Based Glycoproteomics.

Tonini L, Sadet B, Stella A, Bouyssie D, Nigou J, Burlet-Schiltz O Molecules. 2020; 25(10).

PMID: 32443484 PMC: 7287972. DOI: 10.3390/molecules25102348.

References

Kaur D, Lowary T, Vissa V, Crick D, Brennan P . Characterization of the epitope of anti-lipoarabinomannan antibodies as the terminal hexaarabinofuranosyl motif of mycobacterial arabinans. Microbiology (Reading). 2002; 148(Pt 10):3049-3057. DOI: 10.1099/00221287-148-10-3049. View

Nigou J, Gilleron M, Puzo G . Lipoarabinomannans: from structure to biosynthesis. Biochimie. 2003; 85(1-2):153-66. DOI: 10.1016/s0300-9084(03)00048-8. View

Gibson K, Gilleron M, Constant P, Brando T, Puzo G, Besra G . Tsukamurella paurometabola lipoglycan, a new lipoarabinomannan variant with pro-inflammatory activity. J Biol Chem. 2004; 279(22):22973-82. DOI: 10.1074/jbc.M310906200. View

Orholm M, Lundgren J . Improved detection of Pneumocystis carinii by an immunofluorescence technique using monoclonal antibodies. Eur J Clin Microbiol Infect Dis. 1990; 9(12):880-5. DOI: 10.1007/BF01967503. View

Sada E, Aguilar D, Torres M, Herrera T . Detection of lipoarabinomannan as a diagnostic test for tuberculosis. J Clin Microbiol. 1992; 30(9):2415-8. PMC: 265515. DOI: 10.1128/jcm.30.9.2415-2418.1992. View

Elliott A, Namaambo K, Allen B, Luo N, Hayes R, POBEE J . Negative sputum smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka, Zambia. Tuber Lung Dis. 1993; 74(3):191-4. DOI: 10.1016/0962-8479(93)90010-U. View

Shinnick T, Good R . Mycobacterial taxonomy. Eur J Clin Microbiol Infect Dis. 1994; 13(11):884-901. DOI: 10.1007/BF02111489. View

McCloskey N, Turner M, Steffner P, Owens R, Goldblatt D . Human constant regions influence the antibody binding characteristics of mouse-human chimeric IgG subclasses. Immunology. 1996; 88(2):169-73. PMC: 1456430. DOI: 10.1111/j.1365-2567.1996.tb00001.x. View

Mao S, Gao C, Lo C, Wirsching P, Wong C, Janda K . Phage-display library selection of high-affinity human single-chain antibodies to tumor-associated carbohydrate antigens sialyl Lewisx and Lewisx. Proc Natl Acad Sci U S A. 1999; 96(12):6953-8. PMC: 22023. DOI: 10.1073/pnas.96.12.6953. View

10.

De Haard H, van Neer N, Reurs A, Hufton S, Roovers R, Henderikx P . A large non-immunized human Fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies. J Biol Chem. 1999; 274(26):18218-30. DOI: 10.1074/jbc.274.26.18218. View

11.

Boehme C, Molokova E, Minja F, Geis S, Loscher T, Maboko L . Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg. 2005; 99(12):893-900. DOI: 10.1016/j.trstmh.2005.04.014. View

12.

Steingart K, Ng V, Henry M, Hopewell P, Ramsay A, Cunningham J . Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis. 2006; 6(10):664-74. DOI: 10.1016/S1473-3099(06)70602-8. View

13.

Keeler E, Perkins M, Small P, Hanson C, Reed S, Cunningham J . Reducing the global burden of tuberculosis: the contribution of improved diagnostics. Nature. 2006; 444 Suppl 1:49-57. DOI: 10.1038/nature05446. View

14.

Griffith D, Aksamit T, Brown-Elliott B, Catanzaro A, Daley C, Gordin F . An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175(4):367-416. DOI: 10.1164/rccm.200604-571ST. View

15.

Horlacher T, Seeberger P . Carbohydrate arrays as tools for research and diagnostics. Chem Soc Rev. 2008; 37(7):1414-22. DOI: 10.1039/b708016f. View

16.

Schoonbroodt S, Steukers M, Viswanathan M, Frans N, Timmermans M, Wehnert A . Engineering antibody heavy chain CDR3 to create a phage display Fab library rich in antibodies that bind charged carbohydrates. J Immunol. 2008; 181(9):6213-21. DOI: 10.4049/jimmunol.181.9.6213. View

17.

Lim A, Chan C, Wong S, Chan A, Ooi E, Hanson B . Neutralizing human monoclonal antibody against H5N1 influenza HA selected from a Fab-phage display library. Virol J. 2008; 5:130. PMC: 2582236. DOI: 10.1186/1743-422X-5-130. View

18.

McGrath E, McCabe J, Anderson P . Guidelines on the diagnosis and treatment of pulmonary non-tuberculous mycobacteria infection. Int J Clin Pract. 2009; 62(12):1947-55. DOI: 10.1111/j.1742-1241.2008.01891.x. View

19.

Reither K, Saathoff E, Jung J, Minja L, Kroidl I, Saad E . Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis. BMC Infect Dis. 2009; 9:141. PMC: 2741465. DOI: 10.1186/1471-2334-9-141. View

20.

Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D . Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS One. 2010; 5(3):e9848. PMC: 2844421. DOI: 10.1371/journal.pone.0009848. View