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Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats
Authors:Satish P RamachandraRao  Michael A Matthias  Chanthel-Kokoy Mondrogon  Eamon Aghania  Cathleen Park  Casey Kong  Michelle Ishaya  Assael Madrigal  Jennifer Horng  Roni Khoshaba  Anousone Bounkhoun  Fabrizio Basilico  Antonella De Palma  Anna Maria Agresta  Linda Awdishu  Robert K Naviaux  Joseph M Vinetz  Pierluigi Mauri
Abstract:BackgroundInfectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions.ConclusionsWe identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance.
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