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

EMBO Molecular Medicine

Guanghou Shui³  Anne K. Bendt⁷  Ignasius A. Jappar⁷  Hui Ming Lim⁷  Marie Laneelle⁴  Maxime Hervé¹  Laura E. Via²  Gek Huey Chua⁷  Martin W. Bratschi⁷  Siti Zarina Zainul Rahim⁸  Ang Lay Teng Michelle⁸  Soo-Hee Hwang⁶  Jong-Soek Lee⁹  Seok-Yong Eum⁹  Hyun-Kyung Kwak⁹  Mamadou Daffé⁴  Véronique Dartois¹  Gerd Michel⁵  Clifton E. Barry III.² 

[1]Novartis Institute for Tropical Diseases, Singapore

[2]Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland, USA

[3]E-mail address: [4]Département Mécanismes Moléculaires des Infections Mycobactériennes, IPBS-UMR, Toulouse Cedex, France

[5]Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland

[6]National Masan Tuberculosis Hospital, Masan, Republic of Korea

[7]Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore

[8]Department of Microbiology, National University of Singapore, Singapore

[9]International Tuberculosis Research Center, Masan, Republic of Korea

关键词: diagnostic marker;    lipidomics;    mass spectrometry;    Mycobacterium tuberculosis;    mycolic acids;   

DOI  :  10.1002/emmm.201100185

来源: Wiley

【 摘 要 】

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 µl) 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.

【 授权许可】

Unknown   
Copyright © 2012 EMBO Molecular Medicine