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POST-TRANSLATIONAL MODIFICATION OF LIPL32 DURING LEPTOSPIRA INTERROGANS INFECTION
Autor
Afiliación
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University College Dublin. School of Veterinary Medicine. Belfield, Dublin, Ireland
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
Yale 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, Brasil
Yale 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, Brasil
Veterans 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 America
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University College Dublin. School of Veterinary Medicine. Belfield, Dublin, Ireland
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
Yale 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, Brasil
Yale 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, Brasil
Veterans 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 America
University of Victoria. Department of Biochemistry and Microbiology. Victoria, British Columbia, Canada
Resumen en ingles
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.
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