Bittersweet memories: Immunity against Staphylococcus aureus wall teichoic acid

Abstract

Staphylococcus aureus is a leading cause of bacterial infections, including superficial skin infections and bacteremia, which occur both inside and outside the hospital. The emergence of antibiotic-resistant S. aureus strains has increased the need for alternative treatment options, which may be found in boosting host immunity through vaccination. Despite numerous efforts, to this day no effective vaccine exists for S. aureus. It remains incompletely understood what constitutes protective immunity to this bacterium, and which bacterial antigens are the ideal targets for vaccination. Many successful vaccines against other bacterial pathogens, such as the pneumococcal and meningococcal vaccines, target surface-exposed sugars in the bacterial cell wall, specifically the sugar coat (or sugar capsule). For S. aureus however, the sugar capsule failed to provide protection through vaccination. Still, other surface-exposed sugars present in the cell wall of S. aureus are potential targets for vaccination or other immune-based therapies. In this thesis, I describe novel insights into the human immune responses to S. aureus wall teichoic acids (WTAs), abundantly-expressed cell wall sugars. S. aureus WTAs exhibit limited heterogeneity, with three different types currently known (WTA glycotypes). We studied how skin-resident immune cells respond to S. aureus expressing different WTA glycotypes, which is important for rapid activation of the immune system upon S. aureus skin infection. Furthermore, we measured antibody responses to specific WTA glycotypes in healthy individuals and patients with invasive S. aureus infection. We provide rationale that boosting immunity to the WTA sugars may contribute to protective immunity against S. aureus infections.