Post-translational modification of LipL32 during Leptospira interrogans infection.
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, lepto...
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ftdoajarticles:oai:doaj.org/article:51f6d2dc95d64459bc773a48075a0add 2023-05-15T15:12:15+02:00 Post-translational modification of LipL32 during Leptospira interrogans infection. Timothy D Witchell Azad Eshghi Jarlath E Nally Rebecca Hof Martin J Boulanger Elsio A Wunder Albert I Ko David A Haake Caroline E Cameron 2014-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003280 https://doaj.org/article/51f6d2dc95d64459bc773a48075a0add EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4214626?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003280 https://doaj.org/article/51f6d2dc95d64459bc773a48075a0add PLoS Neglected Tropical Diseases, Vol 8, Iss 10, p e3280 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003280 2022-12-31T06:28:13Z 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 tri-methylation. 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 10 e3280 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Timothy D Witchell Azad Eshghi Jarlath E Nally Rebecca Hof Martin J Boulanger Elsio A Wunder Albert I Ko David A Haake Caroline E Cameron Post-translational modification of LipL32 during Leptospira interrogans infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 tri-methylation. 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 ... |
format |
Article in Journal/Newspaper |
author |
Timothy D Witchell Azad Eshghi Jarlath E Nally Rebecca Hof Martin J Boulanger Elsio A Wunder Albert I Ko David A Haake Caroline E Cameron |
author_facet |
Timothy D Witchell Azad Eshghi Jarlath E Nally Rebecca Hof Martin J Boulanger Elsio A Wunder Albert I Ko David A Haake Caroline E Cameron |
author_sort |
Timothy D Witchell |
title |
Post-translational modification of LipL32 during Leptospira interrogans infection. |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003280 https://doaj.org/article/51f6d2dc95d64459bc773a48075a0add |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 10, p e3280 (2014) |
op_relation |
http://europepmc.org/articles/PMC4214626?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003280 https://doaj.org/article/51f6d2dc95d64459bc773a48075a0add |
op_doi |
https://doi.org/10.1371/journal.pntd.0003280 |
container_title |
PLoS Neglected Tropical Diseases |
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8 |
container_issue |
10 |
container_start_page |
e3280 |
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1766342958434484224 |