title: Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever.
abstract: 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.
authors.affiliation: Department of Chemistry, Computational Life Science Cluster, Umeå University, Umeå, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Näsström
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nga Tran
authors.initials: NT
authors.lastname: Vu Thieu
authors.affiliation: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
authors.forename: Sabina
authors.initials: S
authors.lastname: Dongol
authors.affiliation: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Karkey
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Phat
authors.initials: P
authors.lastname: Voong Vinh
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Tuyen
authors.initials: T
authors.lastname: Ha Thanh
authors.affiliation: Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.affiliation: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Department of Chemistry, Computational Life Science Cluster, Umeå University, Umeå, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Antti
mesh_terms: D019540:Area Under Curve; D001426:Bacterial Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D024841:Fluoroquinolones / Q000008:administration & dosage; D008401:Gas Chromatography-Mass Spectrometry; D000077734:Gatifloxacin; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D015999:Multivariate Analysis; D009390:Nepal; D015242:Ofloxacin / Q000008:administration & dosage; D010363:Pattern Recognition, Automated; D025341:Principal Component Analysis; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D012482:Salmonella paratyphi A / Q000378:metabolism*; D012485:Salmonella typhi / Q000378:metabolism*; D014435:Typhoid Fever / Q000097:blood* / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D024841:Fluoroquinolones; D015242:Ofloxacin; D000077734:Gatifloxacin
keywords: Salmonella Paratyphi A; Salmonella Typhi; enteric fever; epidemiology; global health; human; infectious disease; mass spectrometry; metabolites; microbiology; typhoid