Jarlath E Nally1, William Mullen2, John J Callanan3, Harald Mischak2,4, Amaya Albalat5. 1. School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland. 2. BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. 3. Ross University School of Medicine, St. Kitts, West Indies. 4. Mosaiques diagnostics, Hannover, Germany. 5. School of Natural Sciences, University of Stirling, Stirling, UK.
Abstract
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.
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.
Authors: Benjamin A Neely; Katherine C Prager; Alison M Bland; Christine Fontaine; Frances M Gulland; Michael G Janech Journal: J Proteome Res Date: 2018-08-28 Impact factor: 4.466
Authors: Jarlath E Nally; Zbigniew Arent; Darrell O Bayles; Richard L Hornsby; Colm Gilmore; Siobhan Regan; Allan D McDevitt; Jon Yearsley; Séamus Fanning; Barry J McMahon Journal: PLoS Negl Trop Dis Date: 2016-12-09
Authors: Jarlath E Nally; Jennifer H Wilson-Welder; Richard L Hornsby; Mitchell V Palmer; David P Alt Journal: Front Cell Infect Microbiol Date: 2018-03-14 Impact factor: 5.293