Proteomic analysis of urine exosomes reveals renal tubule response to leptospiral colonization in experimentally infected rats

PLoS Neglected Tropical Diseases
Satish P RamachandraRaoPierluigi Mauri

Abstract

Infectious 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. Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also kno...Continue Reading

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Citations

Apr 1, 2016·Molecular BioSystems·Agata AbramowiczMonika Pietrowska
May 2, 2018·Biological & Pharmaceutical Bulletin·Sherif E EmamTatsuhiro Ishida
Feb 28, 2018·Frontiers in Immunology·Wenchao ZhangLijun Tang
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Jun 11, 2019·Critical Care Research and Practice·Linda AwdishuSatish P RamachandraRao

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Methods Mentioned

BETA
biopsy
electrophoresis
light microscopy
PCR
PCA

Software Mentioned

Image J
Thermo Scientific Proteome Discoverer
Graphpad Prism
Multidimensional Algorithm Protein Map ( MAProMa )
SEQUEST
MetaboAnalyst
PLS
DA

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