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 Citations (Scopus)

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

Fingerprint

Mycolic Acids
Tuberculosis
Pharmaceutical Preparations
HIV
Host-Pathogen Interactions
Sensitivity and Specificity
Republic of Korea
Uganda
Vietnam
Rifampin
South Africa
Infection
Sputum
Pulmonary Tuberculosis
Case-Control Studies
Mass Spectrometry
Biomarkers
Bacteria
Lipids
Lung

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., ... 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
Shui, Guanghou ; Bendt, Anne K. ; Jappar, Ignasius A. ; Lim, Hui Ming ; Laneelle, Marie ; Hervé, Maxime ; Via, Laura E. ; Chua, Gek Huey ; Bratschi, Martin W. ; Rahim, Siti Zarina Zainul ; Michelle, Ang Lay Teng ; Hwang, Soo Hee ; Lee, Jong Soek ; Eum, Seok Yong ; Kwak, Hyun Kyung ; Daffé, Mamadou ; Dartois, Véronique ; Michel, Gerd ; Barry, Clifton E. ; Wenk, Markus R. / Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. In: EMBO Molecular Medicine. 2012 ; Vol. 4, No. 1. pp. 27-37.
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Shui, G, Bendt, AK, Jappar, IA, Lim, HM, Laneelle, M, Hervé, M, Via, LE, Chua, GH, Bratschi, MW, Rahim, SZZ, Michelle, ALT, Hwang, SH, Lee, JS, Eum, SY, Kwak, HK, Daffé, M, Dartois, V, Michel, G, Barry, CE & Wenk, MR 2012, 'Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice', EMBO Molecular Medicine, vol. 4, no. 1, pp. 27-37. https://doi.org/10.1002/emmm.201100185

Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. / Shui, Guanghou; Bendt, Anne K.; Jappar, Ignasius A.; Lim, Hui Ming; Laneelle, Marie; Hervé, Maxime; Via, Laura E.; Chua, Gek Huey; Bratschi, Martin W.; Rahim, Siti Zarina Zainul; Michelle, Ang Lay Teng; Hwang, Soo Hee; Lee, Jong Soek; Eum, Seok Yong; Kwak, Hyun Kyung; Daffé, Mamadou; Dartois, Véronique; Michel, Gerd; Barry, Clifton E.; Wenk, Markus R.

In: EMBO Molecular Medicine, Vol. 4, No. 1, 01.01.2012, p. 27-37.

Research output: Contribution to journalArticle

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T1 - Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice

AU - Shui, Guanghou

AU - Bendt, Anne K.

AU - Jappar, Ignasius A.

AU - Lim, Hui Ming

AU - Laneelle, Marie

AU - Hervé, Maxime

AU - Via, Laura E.

AU - Chua, Gek Huey

AU - Bratschi, Martin W.

AU - Rahim, Siti Zarina Zainul

AU - Michelle, Ang Lay Teng

AU - Hwang, Soo Hee

AU - Lee, Jong Soek

AU - Eum, Seok Yong

AU - Kwak, Hyun Kyung

AU - Daffé, Mamadou

AU - Dartois, Véronique

AU - Michel, Gerd

AU - Barry, Clifton E.

AU - Wenk, Markus R.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

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KW - Diagnostic marker

KW - Lipidomics

KW - Mass spectrometry

KW - Mycobacterium tuberculosis

KW - Mycolic acids

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