Elucidation of a human urine metabolite as a seryl-leucine glycopeptide and as a biomarker of eﬀective anti-tuberculosis therapy
CITATION: Fitzgerald, B. L., et al. 2019. Elucidation of a human urine metabolite as a seryl-leucine glycopeptide and as a biomarker of eﬀective anti-tuberculosis therapy. ACS Infectious Diseases, 5(3):353-364, doi:10.1021/acsinfecdis.8b00241.
The original publication is available at https://pubs.acs.org
ENGLISH 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 Oglycosylated 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.