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Diagnostic metabolite biomarkers of chronic typhoid carriage.

Published version
Peer-reviewed

Type

Article

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Authors

Jonsson, Pär 
Johansson, Anders 
Dongol, Sabina 
Karkey, Abhilasha 

Abstract

BACKGROUND: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. METHODOLOGY/PRINCIPAL FINDINGS: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. CONCLUSIONS/SIGNIFICANCE: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.

Description

Keywords

Adult, Aged, Biomarkers, Carrier State, Female, Gallbladder, Gas Chromatography-Mass Spectrometry, Humans, Male, Metabolomics, Middle Aged, Nepal, Plasma, Prospective Studies, Salmonella paratyphi A, Salmonella typhi, Typhoid Fever, Young Adult

Journal Title

PLoS Negl Trop Dis

Conference Name

Journal ISSN

1935-2727
1935-2735

Volume Title

12

Publisher

Public Library of Science (PLoS)
Sponsorship
Wellcome Trust (106158/Z/14/Z)