Comparative plasma high‐resolution metabolomic profiling in patients with drug‐susceptible and multi‐drug resistant pulmonary tuberculosis

Abstract

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.