Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/8809
Title: Post-translational Modification of LipL32 during Leptospira interrogans Infection
Authors: Witchell, Timothy D
Eshghi, Azad
Nally, Jarlath E
Hof, Rebecca
Boulanger, Martin J
Wunder Júnior, Elsio Augusto
Ko, Albert Icksang
Haake, David A
Cameron, Caroline E
Abstract: Background: Leptospirosis, a re-emerging disease of global importance caused by pathogenic Leptospira spp., is considered the world’s most widespread zoonotic disease. Rats serve as asymptomatic carriers of pathogenic Leptospira and are critical for disease spread. In such reservoir hosts, leptospires colonize the kidney, are shed in the urine, persist in fresh water and gain access to a new mammalian host through breaches in the skin. Methodology/Principal Findings: Previous studies have provided evidence for post-translational modification (PTM) of leptospiral proteins. In the current study, we used proteomic analyses to determine the presence of PTMs on the highly abundant leptospiral protein, LipL32, from rat urine-isolated L. interrogans serovar Copenhageni compared to in vitro-grown organisms. We observed either acetylation or tri-methylation of lysine residues within multiple LipL32 peptides, including peptides corresponding to regions of LipL32 previously identified as epitopes. Intriguingly, the PTMs were unique to the LipL32 peptides originating from in vivo relative to in vitro grown leptospires. The identity of each modified lysine residue was confirmed by fragmentation pattern analysis of the peptide mass spectra. A synthetic peptide containing an identified tri-methylated lysine, which corresponds to a previously identified LipL32 epitope, demonstrated significantly reduced immunoreactivity with serum collected from leptospirosis patients compared to the peptide version lacking the trimethylation. Further, a subset of the identified PTMs are in close proximity to the established calcium-binding and putative collagen-binding sites that have been identified within LipL32. Conclusions/Significance: The exclusive detection of PTMs on lysine residues within LipL32 from in vivo-isolated L. interrogans implies that infection-generated modification of leptospiral proteins may have a biologically relevant function during the course of infection. Although definitive determination of the role of these PTMs must await further investigations, the reduced immune recognition of a modified LipL32 epitope suggests the intriguing possibility that LipL32 modification represents a novel mechanism of immune evasion within Leptospira.
keywords: Leptospirose
Leptospira
Leptostirose interrogans
Infecção
Issue Date: 2014
Publisher: Public Library of Science
Citation: WITCHELL, T. D. et al. Post-translational Modification of LipL32 during Leptospira interrogans Infection. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3280, 2014.
ISSN: 1935-2727
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
Witchell TD Post-translational....pdf1.03 MBAdobe PDFView/Open


FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.