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Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice

Shui, G. and Bendt, A. K. and Jappar, I. A. and Lim, H. M. and Laneelle, M. and Herve, M. and Via, L. E. and Chua, G. H. and Bratschi, M. W. and Rahim, S. Z. and Michelle, A. L. and Hwang, S. H. and Lee, J. S. and Eum, S. Y. and Kwak, H. K. and Daffe, M. and Dartois, V. and Michel, G. and Barry, Ceiii and Wenk, M. R.. (2012) Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. EMBO molecular medicine, Vol. 4, H. 1. pp. 27-37.

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Official URL: http://edoc.unibas.ch/dok/A6124665

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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 (200 microl) 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
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Wenk, Markus and Bratschi, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-Blackwell
ISSN:1757-4676
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Aug 2013 07:34
Deposited On:16 Aug 2013 07:29

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