Post-translational Modification of LipL32 during Leptospira interrogans Infection

Detalhes bibliográficos
Autor(a) principal: Witchell, Timothy D
Data de Publicação: 2014
Outros Autores: Eshghi, Azad, Nally, Jarlath E, Hof, Rebecca, Boulanger, Martin J, Wunder Junior, Elsio Augusto, Ko, Albert Icksang, Haake, David A, Cameron, Caroline E
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/8809
Resumo: University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
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spelling Witchell, Timothy DEshghi, AzadNally, Jarlath EHof, RebeccaBoulanger, Martin JWunder Junior, Elsio AugustoKo, Albert IcksangHaake, David ACameron, Caroline E2014-11-12T18:32:07Z2014-11-12T18:32:07Z2014WITCHELL, T. D. et al. Post-translational Modification of LipL32 during Leptospira interrogans Infection. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3280, 2014.1935-2727https://www.arca.fiocruz.br/handle/icict/8809engPublic Library of ScienceLeptospiroseLeptospiraLeptostirose interrogansInfecçãoPost-translational Modification of LipL32 during Leptospira interrogans Infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, CanadaUniversity of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, CanadaUniversity College Dublin. School of Veterinary Medicine. Belfield, Dublin, IrelandUniversity of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, CanadaUniversity of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, CanadaYale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, United States of America / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilYale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, United States of America / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilVeterans Affairs Greater Los Angeles. Healthcare System, Division of Infectious Diseases. Los Angeles, California, United States of America / University of California Los Angeles. David Geffen School of Medicine. Department of Medicine. Los Angeles, California, United States of AmericaUniversity of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, CanadaBackground: 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8809/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALWitchell TD Post-translational....pdfWitchell TD Post-translational....pdfapplication/pdf1051480https://www.arca.fiocruz.br/bitstream/icict/8809/2/Witchell%20TD%20Post-translational....pdf43c37458f6d9e4c40544ce47a1065d35MD52TEXTWitchell TD Post-translational....pdf.txtWitchell TD Post-translational....pdf.txtExtracted texttext/plain54954https://www.arca.fiocruz.br/bitstream/icict/8809/3/Witchell%20TD%20Post-translational....pdf.txt06b56fd6b46d41cbe5271f2ec33da285MD53icict/88092023-03-15 14:33:02.585oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:02Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Post-translational Modification of LipL32 during Leptospira interrogans Infection
title Post-translational Modification of LipL32 during Leptospira interrogans Infection
spellingShingle Post-translational Modification of LipL32 during Leptospira interrogans Infection
Witchell, Timothy D
Leptospirose
Leptospira
Leptostirose interrogans
Infecção
title_short Post-translational Modification of LipL32 during Leptospira interrogans Infection
title_full Post-translational Modification of LipL32 during Leptospira interrogans Infection
title_fullStr Post-translational Modification of LipL32 during Leptospira interrogans Infection
title_full_unstemmed Post-translational Modification of LipL32 during Leptospira interrogans Infection
title_sort Post-translational Modification of LipL32 during Leptospira interrogans Infection
author Witchell, Timothy D
author_facet Witchell, Timothy D
Eshghi, Azad
Nally, Jarlath E
Hof, Rebecca
Boulanger, Martin J
Wunder Junior, Elsio Augusto
Ko, Albert Icksang
Haake, David A
Cameron, Caroline E
author_role author
author2 Eshghi, Azad
Nally, Jarlath E
Hof, Rebecca
Boulanger, Martin J
Wunder Junior, Elsio Augusto
Ko, Albert Icksang
Haake, David A
Cameron, Caroline E
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Witchell, Timothy D
Eshghi, Azad
Nally, Jarlath E
Hof, Rebecca
Boulanger, Martin J
Wunder Junior, Elsio Augusto
Ko, Albert Icksang
Haake, David A
Cameron, Caroline E
dc.subject.other.pt_BR.fl_str_mv Leptospirose
Leptospira
Leptostirose interrogans
Infecção
topic Leptospirose
Leptospira
Leptostirose interrogans
Infecção
description University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-11-12T18:32:07Z
dc.date.available.fl_str_mv 2014-11-12T18:32:07Z
dc.date.issued.fl_str_mv 2014
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/8809
dc.identifier.issn.none.fl_str_mv 1935-2727
identifier_str_mv 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.
1935-2727
url https://www.arca.fiocruz.br/handle/icict/8809
dc.language.iso.fl_str_mv eng
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dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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