Universidad Peruana Cayetano Heredia

Expression of sialic acids and other nonulosonic acids in Leptospira

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dc.contributor.author Ricaldi, J.N.
dc.contributor.author Matthias, M.A.
dc.contributor.author Vinetz, Joseph Michael
dc.contributor.author Lewis, A.L.
dc.date.accessioned 2022-01-18T19:34:35Z
dc.date.available 2022-01-18T19:34:35Z
dc.date.issued 2012
dc.identifier.uri https://hdl.handle.net/20.500.12866/11036
dc.description.abstract Background: Sialic acids are negatively charged nine carbon backbone sugars expressed on mammalian cell surfaces. Sialic acids are part of a larger family of nonulosonic acid (NulO) molecules that includes pseudaminic and legionaminic acids. Microbial expression of sialic acids and other nonulosonic acids has been shown to contribute to host-microbe interactions in a variety of contexts, including participation in colonization, immune subversion, and behaviors such as biofilm formation, autoagglutination and motility. Previous research has suggested that some spirochetes may also express these molecules. Results: Here we use a combination of molecular tools to investigate the presence of NulO biosynthetic gene clusters among clinical and saprophytic isolates of the genus Leptospira. Polymerase chain reaction and Southern blotting suggested that a variety of leptospires encoded NulO biosynthetic pathways. High performance liquid chromatography and mass spectrometry analyses provided biochemical evidence that di-N-acetylated NulO molecules are expressed at relatively high levels by L. interrogans serovar Lai strain 55601, and at lower levels by L. alexanderi serovar Manhao and L. fainei serovar Hurstbridge. Endogenous expression of N-acetylneuraminic acid (Neu5Ac, the most common sialic acid) was documented in L. interrogans serovar Copenhageni strain L1-130. Neu5Ac biosynthesis is also supported by a unique gene fusion event resulting in an enzyme with an N-terminal N-acetylneuraminic acid synthase domain and a C-terminal phosphatase domain. This gene fusion suggests that L. interrogans uses a Neu5Ac biosynthetic pathway more similar to animals than to other bacteria. Analysis of the composition and phylogeny of putative NulO biosynthetic gene clusters in L. interrogans serovar Lai and serovar Copenhageni revealed that both strains have complete biosynthetic pathways for legionamimic acid synthesis, a molecule with the same stereochemistry as sialic acid. Lectin-based affinity purification of NulO-modified molecules, followed by mass spectrometric identification suggests post-translational modification of surface lipoproteins, including Loa22. Conclusions: Leptospira species encode NulO biosynthetic pathways and synthesize multiple NulO molecules including sialic acid. Additional studies are needed to clarify the exact context and functional significance of NulO expression. These findings have implications for immune evasion during systemic leptospirosis. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries BMC Microbiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Animalia en_US
dc.subject nucleotide sequence en_US
dc.subject phylogeny en_US
dc.subject Polymerase Chain Reaction en_US
dc.subject gene expression en_US
dc.subject DNA, Bacterial en_US
dc.subject bacterial strain en_US
dc.subject Leptospira interrogans en_US
dc.subject bacterial colonization en_US
dc.subject biofilm en_US
dc.subject biosynthesis en_US
dc.subject Biosynthetic Pathways en_US
dc.subject Blotting, Southern en_US
dc.subject chemical analysis en_US
dc.subject Chromatography, High Pressure Liquid en_US
dc.subject gene cluster en_US
dc.subject Leptospira en_US
dc.subject Leptospira alexanderi en_US
dc.subject Leptospira fainei serovar Hurstbridge en_US
dc.subject Leptospira interrogans serovar Copenhageni en_US
dc.subject Leptospira interrogans serovar Lai en_US
dc.subject Mammalia en_US
dc.subject Mass Spectrometry en_US
dc.subject n acetylneuraminic acid en_US
dc.subject Nonulosonic acid en_US
dc.subject protein processing en_US
dc.subject Sialic acid en_US
dc.subject spirochete en_US
dc.subject stereochemistry en_US
dc.subject Sugar Acids en_US
dc.title Expression of sialic acids and other nonulosonic acids in Leptospira en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/1471-2180-12-161
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 1471-2180


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