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Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin

Waz, Natalha T. ; Milani, Barbara ; Assoni, Lucas ; Coelho, Guilherme Rabelo ; Sciani, Juliana M. ; Parisotto, Thaís ; Ferraz, Lucio F.C. ; Hakansson, Anders P. LU orcid ; Converso, Thiago R. and Darrieux, Michelle LU (2024) In Scientific Reports 14(1).
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... (More)

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.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cationic peptide, Immune evasion, Indolicidin, Pneumococcal surface protein A, Streptococcus pneumoniae
in
Scientific Reports
volume
14
issue
1
article number
23517
publisher
Nature Publishing Group
external identifiers
  • scopus:85205984587
  • pmid:39384882
ISSN
2045-2322
DOI
10.1038/s41598-024-73564-9
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2024.
id
7ebd2fd7-7a6d-433f-8364-10f69833b96f
date added to LUP
2024-11-27 14:33:58
date last changed
2025-07-10 09:17:28
@article{7ebd2fd7-7a6d-433f-8364-10f69833b96f,
  abstract     = {{<p>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.</p>}},
  author       = {{Waz, Natalha T. and Milani, Barbara and Assoni, Lucas and Coelho, Guilherme Rabelo and Sciani, Juliana M. and Parisotto, Thaís and Ferraz, Lucio F.C. and Hakansson, Anders P. and Converso, Thiago R. and Darrieux, Michelle}},
  issn         = {{2045-2322}},
  keywords     = {{Cationic peptide; Immune evasion; Indolicidin; Pneumococcal surface protein A; Streptococcus pneumoniae}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-73564-9}},
  doi          = {{10.1038/s41598-024-73564-9}},
  volume       = {{14}},
  year         = {{2024}},
}