Abstract
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.
Highlights
Bacterial cell surfaces are decorated by diverse oligosaccharides and glycans in the context of capsules, lipopolysaccharides (LPS), glycoproteins and cell wall–associated glycoconjugates
Little is known about the evolutionary processes and selective forces shaping glycan biosynthetic pathways
Employing comparative genomics and glycan phenotyping, we show that related pgl systems are expressed by all human-restricted Neisseria species but identify unique gene gain and loss events as well as loss-of-function polymorphisms that accommodate a dramatic shift in glycoform structure occurring across the genus
Summary
Bacterial cell surfaces are decorated by diverse oligosaccharides and glycans in the context of capsules, lipopolysaccharides (LPS), glycoproteins and cell wall–associated glycoconjugates. Despite their ubiquity and implicit importance, the evolutionary processes shaping glycan diversity are not fully understood [1]. For capsular polysaccharides and LPS, biosynthetic pathways are typically encoded within contiguous gene clusters. Questions of the evolutionary processes and adaptive potential of glycans apply to bacterial protein glycosylation systems in both their N- and O-linked forms [4] Both dedicated and broadspectrum protein glycosylation are well recognized amongst eubacteria, relatively few studies have comprehensively examined glycan diversity and genotype–phenotype relationships at the genus level [5,6,7,8]
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