title: Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.
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.
authors.affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore. guanghou_shui@nuhs.edu.sg
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Anne K
authors.initials: AK
authors.lastname: Bendt
authors.forename: Ignasius A
authors.initials: IA
authors.lastname: Jappar
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Lim
authors.forename: Marie
authors.initials: M
authors.lastname: Laneelle
authors.forename: Maxime
authors.initials: M
authors.lastname: Hervé
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.forename: Gek Huey
authors.initials: GH
authors.lastname: Chua
authors.forename: Martin W
authors.initials: MW
authors.lastname: Bratschi
authors.forename: Siti Zarina
authors.initials: SZ
authors.lastname: Zainul Rahim
authors.forename: Ang Lay Teng
authors.initials: AL
authors.lastname: Michelle
authors.forename: Soo-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Jong-Soek
authors.initials: JS
authors.lastname: Lee
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Eum
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Kwak
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Véronique
authors.initials: V
authors.lastname: Dartois
authors.forename: Gerd
authors.initials: G
authors.lastname: Michel
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009171:Mycolic Acids / Q000032:analysis*; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013183:Sputum / Q000378:metabolism; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D000904:Antibiotics, Antitubercular; D015415:Biomarkers; D009171:Mycolic Acids; D012293:Rifampin