Bacteria produce many glycosylated structures and polysaccharides, including polysaccharide capsule, teichoic acids, and N- and O-linked glycosylated proteins. The ease of whole genome sequencing has accelerated identification of the involved biosynthesis genes, but experimental data to support a gene-structure relationship is often lacking. By a combination of bacterial mutagenesis, glycoanalysis, bacteriological and immunological in vitro assays and animal infection studies, we aim to elucidate the role of surface glycans in bacterial infectious diseases.
Our lab focuses on infections caused by two important human pathogens, Staphylococcus aureus and Group A Streptococcus (GAS). Both species are common harmless commensals of the skin and naso/pharynx but can also cause life-threatening infections1,2. The composition of the cell wall of S. aureus and GAS is rich in glycans, but their function has remained mostly uncharacterized. For GAS, the dominant cell wall structure consists of the Group A carbohydrate (GAC) or Lancefield antigen, which comprises approximately 50% of the cell wall by weight3. In addition to an essential structural role in the cell wall4, we have demonstrated that the specific N-acetylglucosamine (GlcNAc) epitope of the GAC contributes to pathogenesis5. Similarly, S. aureus expresses several glycosylated structures including GlcNAcylated wall teichoic acid (WTA) 6 and also glycosylated proteins7 that contribute to nasal colonization and systemic infection6,8-10. The molecular mechanism for these virulence-enhancing mechanisms has not been fully elucidated, but insight could open new pathways for selective anti-virulence strategies or vaccine targets to combat these deadly infections.
Considering the dominant presence in the cell wall and location at the host-pathogen interface, we hypothesize that bacterial surface glycans support bacterial survival in the host by either protecting from immune killing or aiding immune evasion. To this end, we work on the following topics:
- Elucidate the biosynthesis pathway of the streptococcal GAC4;
- Study the interaction of glycosylated surface structures with the human immune systems at the molecular level focusing on immune modulation through (C-type) lectin receptors;
- Investigate application of streptococcal carbohydrates as vaccine antigens.