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PLoS Negl Trop Dis. 2014 Oct 30;8(10):e3280. doi: 10.1371/journal.pntd.0003280. eCollection 2014 Oct.

Post-translational modification of LipL32 during Leptospira interrogans infection.

Author information

1
Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
2
School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland.
3
Department of Epidemiology of Microbial Disease, Yale School of Public Health, New Haven, Connecticut, United States of America; Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil.
4
Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.

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 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 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.

PMID:
25356675
PMCID:
PMC4214626
DOI:
10.1371/journal.pntd.0003280
[Indexed for MEDLINE]
Free PMC Article

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