Streptococcus pneumoniae resists host defenses through multiple virulence factors, yet their combined influence on the action of antimicrobial peptides remains unclear. We examined the role of Pneumococcal surface protein A (PspA) and the polysaccharide capsule in modulating susceptibility to the human defensin HNP-1. PspA-deficient strains of two different genetic backgrounds displayed increased sensitivity, while recombinant PspA neutralized peptide activity and anti-PspA antibodies enhanced bacterial killing. The capsule conferred serotype-dependent protection, with type 2 being more effective than type 4, and free polysaccharides acted as decoys by sequestering HNP-1. Removal of surface PspA from capsule-deficient mutants revealed additive contributions of both factors to survival. These findings highlight the complementary roles of capsule and PspA in pneumococcal resistance to HNP-1 and suggest that targeting these mechanisms could potentiate innate immune clearance and provide novel insights that may inform future vaccine design and antimicrobial strategies.
Silva et al. (Mon,) studied this question.
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