Glycan-mediated molecular interactions in bacterial pathogenesis

Abstract

Glycans are expressed on the surface of nearly all host and bacterial cells. Not surprisingly, glycan-mediated molecular interactions play a vital role in bacterial pathogenesis and host responses against pathogens. Glycan-mediated host-pathogen interactions can benefit the pathogen, host, or both. Here, we discuss (i) bacterial glycans that play a critical role in bacterial colonization and/or immune evasion, (ii) host glycans that are utilized by bacteria for pathogenesis, and (iii) bacterial and host glycans involved in immune responses against pathogens. We further discuss (iv) opportunities and challenges for transforming these research findings into more effective antibacterial strategies, and (v) technological advances in glycoscience that have helped to accelerate progress in research. These studies collectively offer valuable insights into new perspectives on antibacterial strategies that may effectively tackle the drug-resistant pathogens that are rapidly spreading globally.

Keywords: anti-bacterial strategies; bacterial pathogens; glycans; glycobiology of host-pathogen interactions; host responses; technological advances in glycoscience.

Figure 1.. Glycointeractions in bacterial pathogenesis.

(A) Bacterial surface glycans play a vital role in adherence and colonization on host cells, which in some cases results in bacterial invasion of host cells. Bacterial glycans are also crucial for biofilm formation. (B) Some bacterial pathogens express molecular mimicry of host glycans on their cell surface (bacteria with pink hexagons) that can disguise themselves from host immune surveillance. Some bacteria cover their cell surface with layers of glycans [capsular polysaccharide (CPS), light pink and/or pink hexagons] to hamper host recognition of common pathogen-associated molecular patterns (PAMPs). In comparison, the recognition of PAMPs (green hexagons) and downstream immune responses is depicted in the right half of the graphic. (C) Many bacterial pathogens and toxins are equipped with lectin-like features that recognize specific host glycans (depicted as a gray rod in the left panel or gray rod with codes for N-glycans in the right) expressed on a set of host cells for their colonization and/or virulence. (D) Conversely, host immune cells can utilize bacterial glycans as molecular patterns to trigger bactericidal immune responses (depicted in the left) and host glycans (blue), resulting in various immune responses and/or pathogen clearance. Multiple pathogens have developed evasion strategies. This review discusses the mechanisms involved.

Figure 2.. Common bacterial glycoconjugates located on bacterial cell surfaces and membranes.

As depicted on the left, the membranes of Gram-positive bacteria consist of the inner membrane (IM) and cell wall comprised of peptidoglycan (PG, a polymer of GlcNAc and MurNAc), capsular polysaccharide (CPS), wall teichoic acid (WTA), and lipoteichoic acid (LTA). As depicted on the right, the membranes of Gram-negative bacteria consist of the PG layer sandwiched between the IM and outer membrane (OM) with the space between the two membranes referred to as the periplasm. The outer surfaces of Gram-negative bacteria are coated by glycans that are part of the lipopolysaccharide (LPS) O-antigen, lipo-oligosaccharide (LOS) core-sugars, and/or the CPS.

Figure 3.. Utilization of host glycans by bacterial pathogens.

Physical barriers to the entry of pathogens (the light blue shaded area in this graphic), including the gastrointestinal (GI) tract, urogenital tract, and respiratory tract, are heavily glycosylated, which is vital for the host barrier function. Paradoxically, those host glycans benefit multiple pathogens for colonization, tropism, and/or as a source of nutrients during infection. Bacterial names and virulence factors involved are indicated in the top portion of this graphic. Some notable examples are highlighted in this figure and are discussed under the heading ‘Host glycans utilized by bacteria for pathogenesis’. Abbreviations: S. Typhimurium, Salmonella enterica serovar Typhimurium; V. cholerae, Vibrio cholerae; UPEC, uropathogenic Escherichia coli; N. meningitidis, Neisseria meningitidis; VCC, Vibrio cholerae cytolysin; RbmC, the biofilm matrix protein.

Figure 4.. Utilization of host glycans by bacterial AB toxins.

Almost all bacterial AB toxins use host glycans as cellular receptors. Toxin names and their glycan receptor moieties identified are indicated in this graphic. The light blue shaded area depicts target host cells. Some notable examples are highlighted in this figure and are discussed under the heading ‘Bacterial toxins’. Abbreviations: LDLR, low-density lipoprotein receptor; sGAGs, sulfated glycosaminoglycans.