Streptococcus pneumoniae evades host cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA

摘要: Streptococcus pneumoniae is a Gram-positive bacterium belonging to the oral streptococcus species, mitis group. This pathogen leading cause of community-acquired pneumonia, which often evades host immunity and causes systemic diseases, such as sepsis meningitis. Previously, we reported that PfbA {beta}-helical cell surface protein contributing pneumococcal adhesion invasion human epithelial cells in addition its survival blood. In present study, investigated role pathogenesis. Phylogenetic analysis indicated pfbA gene specific S. within Our vitro assays showed inhibits neutrophil phagocytosis, survival. We found activates NF-{kappa}B through TLR2, but not TLR4. addition, TLR2/4 inhibitor peptide treatment neutrophils enhanced {Delta}pfbA strain compared control treatment, whereas did affect wild-type strain. mouse pneumonia model, mortality level TNF- bronchoalveolar lavage fluid were comparable between {Delta}pfbA-infected mice, while deletion increased bacterial burden fluid. demonstrated significantly levels plasma, reduced lung liver. These results indicate may contribute success species by inhibiting excess inflammation, mortality.nnImportanceStreptococcus isolated from nasopharynx healthy children, also meningitis, sepsis. this focused on wall anchoring protein, PfbA, pathogenesis pneumoniae-related disease. pneumococcus-specific anti-phagocytic factor functions TLR2 ligand, indicating represent pneumococcal-specific therapeutic target. However, model revealed deficiency burden, decrease mortality. Furthermore, suggest optimizes reproduction regulating PfbA; therefore, inhibition would be an effective strategy for combatting infection. findings underscore challenges involved drug development harboring both commensal pathogenic states.