The glycobiology of microbial infectious disease

Host and microbial glycosylation are critical components in infection and persistent colonization. Many microbial pathogens, including bacteria, fungi, viruses, and parasitic protists, use surface-displayed lectins to target certain cells or tissues to adhere to in the first step of infection, for example, hemagglutinin (HA) on influenzavirus A targets specific sialylated structures on the lungs. Other pathogens display human-like carbohydrate structures on their surface to avoid or modulate the immune response by interactions with host immune receptors, as is the case when lipopolysaccharide (LPS) fucosylation on Helicobacter pylori interacts with the host DC-SIGN receptor to avoid immune response and facilitate persistent colonization. In some cases, this molecular mimicry may lead to the development of autoimmune diseases, such as when Guillain–Barre syndrome is developed post-Campylobacter jejuni infection. On the other hand, this pathogenic arsenal for infection and immune avoidance can also provide therapeutic targets. Polysaccharide capsules on pathogenic bacteria and fungi help pathogens evade the immune system but on the other hand provide effective vaccine candidates, as has been put to good use for the Haemophilus influenzae type b conjugate vaccine. Pathogen lectins can be targeted using carbohydrate derivatives or mimetics to treatments or antiinfectives, such as the sialic acid mimetic drug Relenza targets HA on influenzavirus to treat and prevent influenza. This chapter discusses the involvement of carbohydrate-mediated interactions in bacterial and viral microbial pathogen infection and the modulation of host immune response, and the developments in potential therapeutics and treatments based on these structural interactions. These developments may provide an important source of alternative or complementary drugs as we face a future of ever-increasing antibiotic resistance.