Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever

• Published in: eLife Vol. 3
• Main Authors: Näsström, Elin, Vu Thieu, Nga Tran, Dongol, Sabina, Karkey, Abhilasha, Voong Vinh, Phat, Ha Thanh, Tuyen, Johansson, Anders, Arjyal, Amit, Thwaites, Guy, Dolecek, Christiane, Basnyat, Buddha, Baker, Stephen, Antti, Henrik
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 05-06-2014; eLife Sciences Publications, Ltd
• Subjects: Area Under Curve; Bacterial infections; Bacterial Proteins - metabolism; biomarkers; Biomarkers - metabolism; Case-Control Studies; chemometrics; diagnostics; Disease; enteric fever; Epidemiology and Global Health; Fever; Fluoroquinolones - administration & dosage; Gas chromatography; Gas Chromatography-Mass Spectrometry; Humans; Infections; mass spectrometry; Mass spectroscopy; metabolite; Metabolites; Metabolome; Metabolomics; Microbiology and Infectious Disease; Multivariate Analysis; Nepal; Ofloxacin - administration & dosage; Pathogens; Patients; Pattern recognition; Pattern Recognition, Automated; Principal Component Analysis; Principal components analysis; Randomized Controlled Trials as Topic; ROC Curve; Salmonella; Salmonella Paratyphi A; Salmonella paratyphi A - metabolism; Salmonella Typhi; Salmonella typhi - metabolism; two-dimensional gas chromatography; Typhoid; Typhoid Fever - blood; Typhoid Fever - microbiology; Nepal; global health; enteric fever; epidemiology; infectious disease; typhoid; microbiology; mass spectrometry; Salmonella Typhi; human; metabolites; Salmonella Paratyphi A
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.03100

The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.