Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice
| Autor: | Laura E. Via, Martin W. Bratschi, Soohee Hwang, Hui Ming Lim, Gerd Michel, Mamadou Daffé, Gek Huey Chua, Clifton E. Barry, Hyun-Kyung Kwak, Véronique Dartois, Anne K. Bendt, Marie-Antoinette Lanéelle, Guanghou Shui, Markus R. Wenk, Seokyong Eum, Ignasius A. Jappar, Ang Lay Teng Michelle, Maxime Herve, Jong-Soek Lee, Siti Zarina Zainul Rahim |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Tuberculosis medicine.drug_class Antibiotics HIV Infections Sensitivity and Specificity Microbiology Mycobacterium tuberculosis 03 medical and health sciences Mice Tuberculosis diagnosis Lipidomics medicine Animals Humans Clinical significance Antibiotics Antitubercular Chromatography High Pressure Liquid 030304 developmental biology mass spectrometry Retrospective Studies 0303 health sciences Mice Inbred BALB C biology 030306 microbiology diagnostic marker Sputum biology.organism_classification medicine.disease 3. Good health Mycolic Acids Case-Control Studies Immunology Molecular Medicine lipidomics Female medicine.symptom Rifampin Rifampicin Biomarkers medicine.drug Research Article |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine; Vol 4 |
| ISSN: | 1757-4676 |
| DOI: | 10.1002/emmm.201100185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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