Sweet talking The impact of bacterial glycan diversity on immune sensing

Antibiotic resistance is a growing global health crisis, with mortality rates projected to rise significantly. Opportunistic pathogens Staphylococcus aureus and Streptococcus pyogenes are major contributors to skin and soft tissue infections, yet effective vaccines remain unavailable. This thesis investigates how bacterial surface glycans interact with the human immune system at barrier sites, focusing on Langerhans cells (LCs), immune sentinels in the skin. Understanding local host defenses may indicate why some individuals develop infections while others remain asymptomatic, and inform new therapeutic strategies.
In S. aureus, wall teichoic acids (WTAs) are glycopolymers involved in colonization and immune evasion. Analysis of over 25,000 genomes, which revealed diversity in WTA glycosyltransferases (TarS, TarM, TarP), affecting glycan structures and immune detection. Specific glycosylation patterns may exacerbate inflammation in atopic dermatitis by activating LCs and promoting T helper 2 responses. Single-cell and bulk RNA sequencing identified LC subsets enriched in AD skin, with upregulated pathways linked to prostaglandin signaling, IgE receptor expression, and T cell activation.
In S. pyogenes, the Group A Carbohydrate (GAC) is a conserved cell wall component essential for virulence. Genetic analysis revealed mutations in the gacA–L gene cluster, that altered cell wall composition and immune clearance. Langerin, a C-type lectin receptor on LCs, bound variably to a collection of S. pyogenes strains, and bacterial genes such as emm and mga were found to affect this binding.
Together, these findings highlight the importance of glycan diversity in host–pathogen interactions and provide valuable insights for the development of vaccines and alternative therapies targeting these priority pathogens.