Staphylococcal host adaptation compromises neutrophil killing by concealing bound opsonins with peptidoglycan

The bacterial pathogen Staphylococcus aureus adapts to the host environment by increasing the thickness of its cell wall. However, the impact of cell wall thickening on susceptibility to host defences is unclear. Here, we show that as bacteria adapted to serum, the resulting increase in cell wall thickness led to a reduction in the exposure of bound antibody and complement and a corresponding reduction in phagocytosis and killing by neutrophils. The exposure of opsonins bound to protein antigens or LTA were most significantly reduced, whilst opsonisation by IgG against wall teichoic acid or peptidoglycan was largely unaffected. Partial digestion of accumulated cell wall in host adapted cells using the enzyme lysostaphin restored opsonin exposure and promoted phagocytosis and killing. Concordantly, the antibiotic fosfomycin inhibited cell wall remodelling and maintained full susceptibility of S. aureus to opsonophagocytic killing by neutrophils. These findings reveal that the adaptation of S. aureus to the host environment reduces the ability of the immune system to detect and kill this pathogen through reduced exposure of protein- and LTA-bound opsonins via cell wall remodelling.