Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin
Author
Butantan affiliation
External affiliation
Publication type
Article
Language
English
Access rights
Open access
Terms of use
CC BY-NC-ND
Appears in Collections:
Metrics
Abstract
Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins—cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/5509
Journal title
Keywords
Funding agency
Issue Date
2024
Files in This Item:
Pneumococcal surface protein A prevents killing of streptococcus pneumoniae by indolicidin.pdf
Description:
Size: 1.48 MB
Format: Adobe PDF
View/Open
Description:
Size: 1.48 MB
Format: Adobe PDF
View/Open
This item is licensed under a Creative Commons License