dc.date.accessioned2022-01-18T19:34:35Z
dc.date.available2022-01-18T19:34:35Z
dc.date.created2022-01-18T19:34:35Z
dc.date.issued2012
dc.identifierhttps://hdl.handle.net/20.500.12866/11036
dc.identifierhttps://doi.org/10.1186/1471-2180-12-161
dc.description.abstractBackground: 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.
dc.languageeng
dc.publisherBioMed Central
dc.relationBMC Microbiology
dc.relation1471-2180
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAnimalia
dc.subjectnucleotide sequence
dc.subjectphylogeny
dc.subjectPolymerase Chain Reaction
dc.subjectgene expression
dc.subjectDNA, Bacterial
dc.subjectbacterial strain
dc.subjectLeptospira interrogans
dc.subjectbacterial colonization
dc.subjectbiofilm
dc.subjectbiosynthesis
dc.subjectBiosynthetic Pathways
dc.subjectBlotting, Southern
dc.subjectchemical analysis
dc.subjectChromatography, High Pressure Liquid
dc.subjectgene cluster
dc.subjectLeptospira
dc.subjectLeptospira alexanderi
dc.subjectLeptospira fainei serovar Hurstbridge
dc.subjectLeptospira interrogans serovar Copenhageni
dc.subjectLeptospira interrogans serovar Lai
dc.subjectMammalia
dc.subjectMass Spectrometry
dc.subjectn acetylneuraminic acid
dc.subjectNonulosonic acid
dc.subjectprotein processing
dc.subjectSialic acid
dc.subjectspirochete
dc.subjectstereochemistry
dc.subjectSugar Acids
dc.titleExpression of sialic acids and other nonulosonic acids in Leptospira
dc.typeinfo:eu-repo/semantics/article


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