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Elucidation of a Human Urine Metabolite as a Seryl-Leucine Glycopeptide and as a Biomarker of Effective Anti-Tuberculosis Therapy.

Authors
  • Fitzgerald, Bryna L1
  • Islam, M Nurul1
  • Graham, Barbara1
  • Mahapatra, Sebabrata1
  • Webb, Kristofor1
  • Boom, W Henry2, 3
  • Malherbe, Stephanus T4
  • Joloba, Moses L5
  • Johnson, John L2, 3
  • Winter, Jill6
  • Walzl, Gerhard4
  • Belisle, John T1
  • 1 Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology , Colorado State University , 200 West Lake Street, 0922 Campus Delivery , Fort Collins , Colorado 80523 , United States. , (United States)
  • 2 Department of Medicine, Tuberculosis Research Unit (TBRU) , Case Western Reserve University , 10900 Euclid Avenue , Cleveland , Ohio 44106 , United States. , (United States)
  • 3 Uganda-Case Western Reserve University Research Collaboration , 28A Upper Kololo Terrace , Kampala , Uganda. , (Uganda)
  • 4 DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , Stellenbosch University , P.O. Box 241, Francie van Zijl Drive , Cape Town 8000 , South Africa. , (South Africa)
  • 5 School for Biomedical Sciences , Makerere University , P.O. Box 7062, Kampala , Uganda. , (Uganda)
  • 6 Catalysis Foundation for Health , 2100 Addison Street , Berkeley , California 94704 , United States. , (United States)
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Mar 08, 2019
Volume
5
Issue
3
Pages
353–364
Identifiers
DOI: 10.1021/acsinfecdis.8b00241
PMID: 30585483
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The evaluation of new tuberculosis (TB) therapies is limited by the paucity of biomarkers to monitor treatment response. Previous work detected an uncharacterized urine metabolite with a molecular mass of 874.3547 Da that showed promise as a biomarker for successful TB treatment. Using mass spectrometry combined with enzymatic digestions, the metabolite was structurally characterized as a seryl-leucine core 1 O-glycosylated peptide (SLC1G) of human origin. Examination of SLC1G in urine revealed a significant abundance increase in individuals with active TB versus their household contacts and healthy controls. Moreover, differential decreases in SLC1G levels were observed by week one in TB patients during successful treatment versus those that failed treatment. The SLC1G levels were also associated with clinical parameters used to measure bacterial burden (GeneXpert) and inflammation (positron emission tomography-computed tomography (PET-CT)). These results demonstrate the importance of metabolite identification and provide strong evidence for applying SLC1G as a biomarker of TB treatment response.

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