Abstract
Pneumococcal strains are variably resistant to killing by neutrophil extracellular traps (NETs). We hypothesize that this variability in resistance is due to heterogeneity in pneumococcal surface protein A (PspA), a structurally diverse virulence factor of Streptococcus pneumoniae. Pneumococcal strains showed variability in induction of NETs and in susceptibility to killing by NETs. The variability in susceptibility to NETs-mediated killing of pneumococcal strains is attributed to PspA, as strains lacking the surface expression of PspA were significantly more sensitive to NETs-mediated killing compared to the wild-type strains. Using pspA switch mutants we were further able to demonstrate that NETs induction and killing by NETs is a function of PspA as mutants with switch PspA demonstrated donor phenotype. Antibody to PspA alone showed an increase in induction of NETs, and NETs thus generated were able to trap and kill pneumococci. Pneumococci opsonized with antibody to PspA showed increase adherence to NETs but a decrease susceptibility to killing by NETs. In conclusion we demonstrate a novel role for pneumococcal PspA in resisting NETs mediated killing and allowing the bacteria to escape containment by blocking binding of pneumococci to NETs.
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