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

Guanghou Shui, Anne K. Bendt, Ignasius A. Jappar, Hui Ming Lim, Marie Laneelle, Maxime Hervé, Laura E. Via, Gek Huey Chua, Martin W. Bratschi, Siti Zarina Zainul Rahim, Ang Lay Teng Michelle, Soo Hee Hwang, Jong Soek Lee, Seok Yong Eum, Hyun Kyung Kwak, Mamadou Daffé, Véronique Dartois, Gerd Michel, Clifton E. Barry, Markus R. Wenk

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalEMBO Molecular Medicine
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine

Keywords

  • Diagnostic marker
  • Lipidomics
  • Mass spectrometry
  • Mycobacterium tuberculosis
  • Mycolic acids

Cite this

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). Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. EMBO Molecular Medicine, 4(1), 27-37. https://doi.org/10.1002/emmm.201100185