The Renaissance of Bacillosamine and Its Derivatives: Pathway Characterization and Implications in Pathogenicity

Abstract

Prokaryote-specific sugars, including N,N´-diacetylbacillosamine (diNAcBac) and pseudaminic acid, have experienced a renaissance in the past decade due to their discovery in glycans related to microbial pathogenicity. DiNAcBac is found at the reducing end of oligosaccharides of N- and O-linked bacterial protein glycosylation pathways of Gram-negative pathogens including Campylobacter jejuni and Neisseria gonorrhoeae. Further derivatization of diNAcBac results in the nonulosonic acid known as legionaminic acid, which was first characterized in the O-antigen of the lipopolysaccharide (LPS) in Legionella pneumophila. Pseudaminic acid, an isomer of legionaminic acid, is also important in pathogenic bacteria such as Helicobacter pylori due to its occurrence in O-linked glycosylation of flagellin proteins, which plays an important role in flagellar assembly and motility. Here, we present recent advances in the characterization of the biosynthetic pathways leading to these highly modified sugars and investigation of the roles that each plays in bacterial fitness and pathogenicity.

Diversity Within the O-linked Protein Glycosylation Systems of Acinetobacter Species

“…Although the identities of these residues cannot be confirmed from the mass alone the convergence of similar residues, irrespective of their stereochemistry, is an observation of significant note. A similar concept of the utilization of a conserved carbohydrate repertoire has been noted within Neisseria and Campylobacter species where both systems utilize diBacNAc yet the enzymes responsible for the generation of diBacNAc represent two phylogenetically distinct clades (62)(63)(64). Widespread use of these unique carbohydrates by multiple bacterial glycosylation systems suggests preference for these sugars in protein modification, although the exact advantages of these residues are unknown.…”

Tannerella forsythiastrains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications

“…It is established knowledge that Sias play crucial roles in the life-cycles of various organisms from eukaryotes to prokaryotes (Varki et al 2009). While Sias are commonly present as terminal residues of many eukaryotic glycoconjugates and have also been identified in several prokaryotic polysaccharides, a number of NulOs appear to be unique to bacterial species (Knirel et al 2003; Morrison and Imperiali 2014; Zunk and Kiefel 2014; Kenyon et al 2015; Schäffer and Messner 2016). Due to their structural and biosynthetic similarities to Sia, these NulOs are also often referred to as Sia-like sugars (Figure 1A), the most studied of which are pseudaminic acids (such as 5,7-diacetamido-3,5,7,9-tetradeoxy- l - glycero - l - manno -NulO, Pse5,7Ac 2 ) and legionaminic acids (such as 5,7-diacetamido-3,5,7,9-tetradeoxy- d - glycero - d - galacto -NulO, Leg5,7Ac 2 ).…”

Giant Virus Megavirus chilensis Encodes the Biosynthetic Pathway for Uncommon Acetamido Sugars

“…For all of the experiments, 512 FIDs of 2,048 complex data points were collected, 32 scans/FID were acquired for homonuclear spectra, and a mixing time of 100 ms was used for total correlation spectroscopy spectrum acquisition. The gradient heteronuclear single quantum coherence spectrum was acquired with 50 scans/FID, and the GARP sequence was used for 13 C decoupling during acquisition; gradient heteronuclear multiple bond coherence scans doubled those of the gradient heteronuclear single quantum coherence spectrum. Data processing and analysis were performed with Bruker Topspin 3 program.…”

“…Two different types of enzymes have been identified. In one case, this step is a simple dehydration with formation of UDP-2-acetamido-2,6-dideoxy-␣-D-xylo-4-hexulose, which is typical of the UDP-bacillosamine or UDP-Nacetyl-D-fucosamine (UDP-D-FucNAc) 5 and UDP-N-acetyl-Dquinovosamine (UDP-D-QuiNAc) pathways (13,14). In other cases, the enzymes are "inverting" 4,6-dehydratases, catalyzing also the epimerization of C-5, with the consequent inversion of the D-configuration to L-, and the formation of UDP-2-acetamido-2,6-dideoxy-␤-L-arabino-4-hexulose (Fig.…”

“…1). This reaction is catalyzed by PseB/FlaA1 in the case of the pseudaminic acid (Pse) pathway, where the transfer of an amino group to the C-4 carbonyl follows this first step (13). On the other hand, several enzymes are involved in the formation of 2-acetamido-2,6-dideoxy-L-hexoses (Fig.…”