Bacterial Glycosidases in Pathogenesis and Glycoengineering

Abstract

Glycosylation is a common post-translational protein modification and many key proteins of the immune system are glycosylated. As the true experts of our immune system, pathogenic bacteria produce enzymes that can modify the carbohydrates (glycans) of the defense mechanisms in order to favor bacterial survival and persistence. At the intersection between bacterial pathogenesis and glycobiology, there is an increased interest in studying the bacterial enzymes that modify the protein glycosylation of their colonized or infected hosts. This is of great importance in order to fully understand bacterial pathogenesis, but it also presents itself as a valuable source for glycoengineering and glycoanalysis tools. This article highlights the role of bacterial glycosidases during infections, introduces the use of such enzymes as glycoengineering tools and discusses the potential of further studies in this emerging field.

Mass spectrometry for protein sialoglycosylation

“…Unlike PNGases, endo‐ O ‐glycosidases usually act on the α‐linked disaccharide, while show little or no activity for releasing larger glycan chains. These enzymes mainly cleave Core 1 O ‐linked glycan (Galβ1,3GalNAc), and in only a few cases they fully hydrolyze Core 3 O ‐linked disaccharide (GlcNAcβ1,3GalNAc) . Hence, the sialic acid, lactosamine or fucose attached to the disaccharide should be removed to unmask core structures prior to cleavage using O ‐glycosidases.…”

CP40 from Corynebacterium pseudotuberculosis is an endo-β-N-acetylglucosaminidase

“…Bacterial endoglycosidases has been extensively used as tools in glycobiology research, but have been somewhat overlooked in pathogenesis research [10]. However, since glycobiology of the immune system, or glycoimmunology, is getting more attention, bacterial modification of glycoproteins beyond mere nutrient acquisition is indeed relevant to study in detail [9].…”

“…Numerous glycosidases from bacterial pathogens with activity on mammalian glycoproteins have been identified and characterized [9]. Some of these glycosidases are used for glycan engineering and glycan analysis of glycoproteins, or as tools for glycobiology research and drug development [10]. Endoglycosidases F 1 , F 2 and F 3 are important glycosidases from Elizabethkingia meningoseptica (formerly Flavobacterium meningosepticum ) have been used as standard tools for glycoprotein characterization and glycoengineering.…”

“…These endo-β- N -acetylglucosaminidases hydrolyze β-1,4- N- acetyl- D -glucosamine linkages in the chitobiose core of N- glycans in glycoproteins [11]. Although PNGase F is an amidase and not a glycosidase, it is often used in this context as an important tool able to release most eukaryotic N-glycans by catalyzing the hydrolysis of the amide bond between the reducing end N -acetylglucosamine (GlcNAc) and the asparagine residue of the glycoprotein [10, 11]. …”

EndoSd: An IgG Glycan Hydrolyzing Enzyme in Streptococcus Dysgalactiae Subspecies Dysgalactiae

“…EndoS is also used as a tool to analyze and/or modify glycans on antibodies [15,[23][24]. In addition, EndoS has been shown to selectively deactivate serum IgG, thus allowing an EndoS-resistant engineered oligomannose monoclonal antibody to interact better with FcRs [7].…”