Detection of urinary biomarkers in reservoir hosts of leptospirosis by capillary electrophoresis-mass spectrometry

Purpose: Pathogenic leptospires colonize the renal tubules of reservoir hosts of infection and are excreted via urine into the environment. Asymptomatic reservoir hosts include a wide range of domestic and wild animal species and include cattle, dogs, and rats that can persistently excrete large numbers of pathogenic leptospires over many months. A similar presentation has been observed in humans categorized as "long-term asymptomatic individuals" as they excreted leptospires in the absence of any clinical symptoms or positive serology. Experimental design: In the current study, the urine of experimentally infected rats, which showed no clinical signs or positive serology, was analyzed by CE-MS to identify urinary biomarkers of chronic infection. Results: A discriminating peptide pattern of 43 polypeptides provided a sensitivity of 93%, a specificity of 83%, and an accuracy of 90% for the identification of urine from chronically infected rats (p < 0.05, AUC > 90%). The majority of discriminating peptides were decreased in abundance in urine of chronically infected rats, including a peptide derived from neprilysin, a membrane metalloendopeptidase, the expression of which has previously been shown to be diminished in infected urine. Conclusion and clinical relevance: Results highlight the diagnostic capabilities of urinary biomarkers to identify reservoir hosts of leptospirosis using CE coupled to MS.