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Title: Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice
Authors: Shui, G. 
Bendt, A.K.
Jappar, I.A.
Lim, H.M.
Laneelle, M.
Hervé, M.
Via, L.E.
Chua, G.H.
Bratschi, M.W.
Rahim, S.Z.Z.
Michelle, A.L.T.
Hwang, S.-H.
Lee, J.-S.
Eum, S.-Y.
Kwak, H.-K.
Daffé, M.
Dartois, V.
Michel, G.
Barry, C.E.
Wenk, M.R.
Keywords: Diagnostic marker
Mass spectrometry
Mycobacterium tuberculosis
Mycolic acids
Issue Date: Jan-2012
Citation: Shui, G., Bendt, A.K., Jappar, I.A., Lim, H.M., Laneelle, M., Hervé, M., Via, L.E., Chua, G.H., Bratschi, M.W., Rahim, S.Z.Z., Michelle, A.L.T., Hwang, S.-H., Lee, J.-S., Eum, S.-Y., Kwak, H.-K., Daffé, M., Dartois, V., Michel, G., Barry, C.E., Wenk, M.R. (2012-01). Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. EMBO Molecular Medicine 4 (1) : 27-37. ScholarBank@NUS Repository.
Abstract: Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection because they are bacteria-derived, contain information about bacterial species, modulate host-pathogen interactions and are chemically inert. Here, we present a novel approach based on mass spectrometry. Quantification of specific precursor→fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity. We next used this tool in a retrospective case-control study of patients with pulmonary TB with varying disease burdens from South Korea, Vietnam, Uganda and South Africa. MAs were extracted from small volume sputum (200μl) and analysed without the requirement for derivatization. Infected patients (70, 19 of whom were HIV+) could be separated from controls (40, 20 of whom were HIV+) with a sensitivity and specificity of 94 and 93%, respectively. Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment. Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection. © 2012 EMBO Molecular Medicine.
Source Title: EMBO Molecular Medicine
ISSN: 17574676
DOI: 10.1002/emmm.201100185
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