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Comparative plasma high‐resolution metabolomic profiling in patients with drug‐susceptible and multi‐drug resistant pulmonary tuberculosis
Author(s) -
Frediani Jennifer,
Chong Elizabeth,
Jones Dean,
Yu Tianwei,
Zhang Lifan,
Tukvadze Nestani,
Sanikidze Ekaterina,
Kipiani Maia,
Hebbar Gautam,
Tran Vilinh,
Kempker Russell,
Tangpricha Vin,
Blumberg Henry,
Ziegler Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.748.1
Subject(s) - metabolite , tuberculosis , metabolomics , mycobacterium tuberculosis , metabolome , medicine , logistic regression , drug , glycan , pharmacology , chemistry , biochemistry , pathology , chromatography , glycoprotein
Background Mycobacterium ( Mtb ) cell wall structure is poorly understood, especially in multi‐drug resistant tuberculosis (MDR‐TB). Methods: Plasma from 23 patients with MDR‐TB (34±9 yrs old; 46% male) and 45 age‐ and gender‐matched patients with drug‐susceptible TB (DS‐TB) were obtained within 7 days of TB diagnosis. Plasma was analyzed using high‐resolution LC‐MS. A metabolome‐wide association study was carried out through simultaneous logistic regression models with MDR‐TB/DS‐TB status as the dependent variable and the log‐concentration of metabolites as the independent variable. Each regression model was adjusted for age, gender, BMI and income. R (3.1.0) and Mummichog (0.10.3) were used for metabolite and pathway analysis. Metabolites with raw p‐values 蠄 0.05 in the regression models were included. Results: Of 5,716 metabolites detected, 66 were significantly different between MDR‐TB and DS‐TB (raw p‐value=0.02). Pathway analysis revealed niacin metabolism and N‐glycan biosynthesis as significant distinguishing pathways. Putative matches in the N‐glycan biosynthesis pathway included dolichyl phosphate D‐mannose ( m/z ‐131.0212) and isopentenyl diphosphate ( m/z ‐135.0018), each upregulated in the MDR‐TB group. Conclusions This pilot study revealed potential Mtb cell wall N‐glycan specific metabolites that are upregulated in MDR‐TB subjects when compared to DS‐TB subjects.