Host-induced cell wall remodeling impairs opsonophagocytosis of by neutrophils.

UNLABELLED

The bacterial pathogen responds to the host environment by increasing the thickness of its cell wall. However, the impact of cell wall thickening on susceptibility to host defenses is unclear. Using bacteria incubated in human serum, we show that host-induced increases 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 lipoteichoic acid (LTA) was most significantly reduced, while opsonization by IgG against wall teichoic acid or peptidoglycan was largely unaffected. Partial digestion of accumulated cell wall using the enzyme lysostaphin restored opsonin exposure and promoted phagocytosis and killing. Concordantly, the antibiotic fosfomycin inhibited cell wall remodeling and maintained the full susceptibility of to opsonophagocytic killing by neutrophils. These findings reveal that host-induced changes to the cell wall reduce the ability of the immune system to detect and kill this pathogen through reduced exposure of protein- and LTA-bound opsonins.

IMPORTANCE

Understanding how bacteria adapt to the host environment is critical in determining fundamental mechanisms of immune evasion, pathogenesis, and the identification of targets for new therapeutic approaches. Previous work demonstrated that remodels its cell envelope in response to host factors and we hypothesized that this may affect recognition by antibodies and thus killing by immune cells. As expected, incubation of in human serum resulted in rapid binding of antibodies. However, as bacteria adapted to the serum, the increase in cell wall thickness resulted in a significant reduction in exposure of bound antibodies. This reduced antibody exposure, in turn, led to reduced killing by human neutrophils. Importantly, while antibodies bound to some cell surface structures became obscured, this was not the case for those bound to wall teichoic acid, which may have important implications for vaccine design.