Bacterial Glycans
Bacterial glycans are essential in the colonization of bacteria, invasion of host tissues, and modulation of immune responses in the gut104. Glycoconjugates produced by bacteria include LPS, teichoic acids, glycoproteins, glycolipids, peptidoglycans, and capsular polysaccharides233. Some species, such asPseudomonas aeruginosa and Neisseria meningitidis express O-linked glycoproteins, mainly found in pilin and flagellin subunits, and other species, such as Haemophilus influenzae express N-linked glycoproteins234,235. L. plantarum , a commensal bacterium, expresses an O-glycosylated protein, Acm2, as its major autolysin236 . The glycosylation machinery in C. jejuni mostly relies on oligosaccharyltransferase PglB, which transfers oligosaccharides to proteins237.C. jejuni deficient in PglB have attenuated pathogenesis, highlighting the microbe’s reliance on its glycosylation system238.
Bacterial surface glycans can be recognized by immune cells239. One example is when the glycans expressed by bacteria are recognized by host lectins such as CLRs, galectins, and Siglecs. This recognition may result in the engulfment of the microbe by DCs, allowing for the processing and presentation of immunogenic epitopes103,240,241. Zwitterionic polysaccharide (ZPS) capsules in bacteria are highly studied immunomodulatory bacterial glycans, which play many important roles in the regulation of intestinal immune homeostasis242. For example, Polysaccharide A (PSA) of B. fragilis , a ZPS, induces the production of IL-10 through APCs and thereby creates a tolerogenic environment to colonize243. It can also skew the T-helper balance in favor of Th1 and help maintain the Th1/Th2 balance in the gut80. Bacteria can also mimic host glycan structures (molecular mimicry)152,244. Bacteria like B. fragilis can use the free fucose on their capsule and imitate the fucosylated epithelial glycans245. This process also aids in immune evasion of the bacteria152.
Apart from expressing glycans on their surface, gut bacteria also produce enzymes that modulate glycan expression on immune cells103. For example, immune evasion byStreptococcus pyogenes (Group A streptococcus), a pathogen that causes diseases like acute rheumatic fever and post-streptococcal glomerulonephritis, is attained by direct glycan modulation on antibodies246,247. A targeted mass spectrometry study has shown that this is achieved by an endoglycosidase, EndoS, that cleaves the conserved N-glycan on IgG antibodies246.