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• Wang, Nelson; Anonsen, Jan Haug; Hadjineophytou, Chris; Reinar, William Brynildsen; Børud, Bente & Vik, Åshild [Show all 7 contributors for this article] (2020). Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria. Glycobiology. ISSN 0959-6658. doi: 10.1093/glycob/cwaa073. Full text in Research Archive Show summary

  Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease. Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species. However, there are inconsistencies between pgl gene status and observed glycan structures. One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp. glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide. Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds. Moreover, PglG function in N. elongata subsp. glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis. We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp. glycolytica. The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species. Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes. Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.

• Wang, Nelson; Anonsen, Jan Haug; Viburiene, Raimonda; Lam, Joseph S; Vik, Åshild & Koomey, Michael (2019). Disrupted synthesis of a di-N-acetylated sugar perturbs mature glycoform structure and microheterogeneity in the O-linked protein glycosylation system of Neisseria elongata subsp. glycolytica. Journal of Bacteriology. ISSN 0021-9193. 201(1). doi: 10.1128/JB.00522-18. Full text in Research Archive
• Hadjineophytou, Chris; Anonsen, Jan Haug; Wang, Nelson; Ma, Kevin; Viburiene, Raimonda & Vik, Åshild [Show all 10 contributors for this article] (2019). Genetic determinants of genus-level glycan diversity in a bacterial protein glycosylation system. PLoS Genetics. ISSN 1553-7390. 15(12), p. 1–24. doi: 10.1371/journal.pgen.1008532. Full text in Research Archive Show summary

  The human pathogens N. gonorrhoeae and N. meningitidis display robust intra- and interstrain glycan diversity associated with their O-linked protein glycosylation (pgl) systems. In an effort to better understand the evolution and function of protein glycosylation operating there, we aimed to determine if other human-restricted, Neisseria species similarly glycosylate proteins and if so, to assess the levels of glycoform diversity. Comparative genomics revealed the conservation of a subset of genes minimally required for O-linked protein glycosylation glycan and established those pgl genes as core genome constituents of the genus. In conjunction with mass spectrometric–based glycan phenotyping, we found that extant glycoform repertoires in N. gonorrhoeae, N. meningitidis and the closely related species N. polysaccharea and N. lactamica reflect the functional replacement of a progenitor glycan biosynthetic pathway. This replacement involved loss of pgl gene components of the primordial pathway coincident with the acquisition of two exogenous glycosyltransferase genes. Critical to this discovery was the identification of a ubiquitous but previously unrecognized glycosyltransferase gene (pglP) that has uniquely undergone parallel but independent pseudogenization in N. gonorrhoeae and N. meningitidis. We suggest that the pseudogenization events are driven by processes of compositional epistasis leading to gene decay. Additionally, we documented instances where inter-species recombination influences pgl gene status and creates discordant genetic interactions due ostensibly to the multi-locus nature of pgl gene networks. In summary, these findings provide a novel perspective on the evolution of protein glycosylation systems and identify phylogenetically informative, genetic differences associated with Neisseria species.

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• Wang, Nelson; Anonsen, Jan Haug; Vik, Åshild & Koomey, Michael (2018). Functional analyses of a glycosyltransferase reveal a genus-wide trajectory for glycan evolution in a bacterial protein glycosylation system. Full text in Research Archive
• Escalante, Hugo; Wan, Jun & Riegler, Michael (2017). IAPR Newsletter. Full text in Research Archive
• Wang, Nelson; Anonsen, Jan Haug; Viburiene, Raimonda; Lam, Joseph S; Vik, Åshild & Koomey, Michael (2016). Identification and analyses of pgl genes required for tetrasaccharide biosynthesis in Neisseria elongata subsp. glycolytica reveals patterns of protein glycosylation evolution at the genus level. Full text in Research Archive
• Wang, Nelson (2015). Bacterial Protein Glycosylation: an Evolutionary Perspective from the genus Neisseria. Full text in Research Archive

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