Autor(es)

Waz, Natalha T. ; Milani, Barbara ; Assoni, Lucas ; Coelho, Guilherme Rabelo ; Sciani, Juliana M. ; Parisotto, Thais ; Ferraz, Lucio F. C. ; Hakansson, Anders P. ; Converso, Thiago R. ; Darrieux, Michelle

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 14, n. 1, p. 10-pg., 2024-10-09.

Resumo

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. (AU)

• Processo FAPESP: 23/10579-8 - AVALIAÇÃO DE SUBUNIDADES DAS FIMBRIAS TIPOS I E III COMO CANDIDATOS VACINAIS CONTRA INFECÇÃO POR Klebsiella pneumoniae
• Beneficiário: Michelle Darrieux Sampaio Bertoncini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/11037-6 - Resistência de Streptococcus pneumoniae a peptídeos antimicrobianos catiônicos: papel da cápsula polissacarídica e da proteína de superfície de pneumococo A
• Beneficiário: Michelle Darrieux Sampaio Bertoncini
• Modalidade de apoio: Auxílio à Pesquisa - Regular