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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
09 10 2024
Historique:
received: 11 04 2024
accepted: 18 09 2024
medline: 10 10 2024
pubmed: 10 10 2024
entrez: 9 10 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39384882
doi: 10.1038/s41598-024-73564-9
pii: 10.1038/s41598-024-73564-9
doi:

Substances chimiques

pneumococcal surface protein A 0
indolicidin 073SBV429N
Bacterial Proteins 0
Lactoferrin EC 3.4.21.-
Antimicrobial Cationic Peptides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23517

Subventions

Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : 88887.901630/2023-00
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : 88887.148363/2017-00
Organisme : Svenska Forskningsrådet Formas
ID : 2021-06050
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2023/10579-8

Informations de copyright

© 2024. The Author(s).

Références

Subramanian, K., Henriques-Normark, B. & Normark, S. Emerging concepts in the pathogenesis of the Streptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen. Cell. Microbiol. 21, e13077. https://doi.org/10.1111/cmi.13077 (2019).
doi: 10.1111/cmi.13077 pubmed: 31251447 pmcid: 6899785
Collaborators, G. L. R. I. & Global Burden of Disease Lower Respiratory Infections Collaborators. Estimates of the Global, Regional, and National Morbidity, Mortality, and aetiologies of Lower Respiratory infections in 195 Countries 1990–2016: a systematic analysis for the global burden of Disease Study 2016. Lancet Infect. Dis. 18 (1191–1210). https://doi.org/10.1016/S1473-3099(18)30310-4 (2018). (2016).
Converso, T. R., Assoni, L., Andre, G. O., Darrieux, M. & Leite, L. C. C. The long search for a serotype independent pneumococcal vaccine. Expert Rev. Vaccines. 19, 57–70. https://doi.org/10.1080/14760584.2020.1711055 (2020).
doi: 10.1080/14760584.2020.1711055 pubmed: 31903805
Converso, T. R., Goulart, C., Rodriguez, D., Darrieux, M. & Leite, L. C. C. Rational selection of broadly cross-reactive family 2 PspA molecules for inclusion in chimeric pneumococcal vaccines. Microb. Pathog. 109, 233–238. https://doi.org/10.1016/j.micpath.2017.06.004 (2017).
doi: 10.1016/j.micpath.2017.06.004 pubmed: 28602840
Andre, G. O. et al. Role of Streptococcus pneumoniae proteins in evasion of complement-mediated immunity. Front. Microbiol. 8, 224. https://doi.org/10.3389/fmicb.2017.00224 (2017).
doi: 10.3389/fmicb.2017.00224 pubmed: 28265264 pmcid: 5316553
Ren, B. et al. The virulence function of Streptococcus pneumoniae surface protein A involves inhibition of complement activation and impairment of complement receptor-mediated protection. J. Immunol. 173, 7506–7512. https://doi.org/10.4049/jimmunol.173.12.7506 (2004).
doi: 10.4049/jimmunol.173.12.7506 pubmed: 15585877
Ren, B., Szalai, A. J., Thomas, O., Hollingshead, S. K. & Briles, D. E. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect. Immun. 71, 75–85. https://doi.org/10.1128/IAI.71.1.75-85.2003 (2003).
doi: 10.1128/IAI.71.1.75-85.2003 pubmed: 12496151 pmcid: 143380
Tu, A. H., Fulgham, R. L., McCrory, M. A., Briles, D. E. & Szalai, A. J. Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. Infect. Immun. 67, 4720–4724. https://doi.org/10.1128/IAI.67.9.4720-4724.1999 (1999).
doi: 10.1128/IAI.67.9.4720-4724.1999 pubmed: 10456922 pmcid: 96800
Hakansson, A. et al. Characterization of binding of human lactoferrin to pneumococcal surface protein A. Infect. Immun. 69, 3372–3381. https://doi.org/10.1128/IAI.69.5.3372-3381.2001 (2001).
doi: 10.1128/IAI.69.5.3372-3381.2001 pubmed: 11292760 pmcid: 98296
Hammerschmidt, S., Bethe, G., Remane, P. H. & Chhatwal, G. S. Identification of pneumococcal surface protein A as a lactoferrin-binding protein of Streptococcus pneumoniae. Infect. Immun. 67, 1683–1687 (1999).
doi: 10.1128/IAI.67.4.1683-1687.1999 pubmed: 10085004 pmcid: 96514
Lu, J. et al. Lactoferrin: A critical mediator of both Host Immune Response and Antimicrobial Activity in response to streptococcal infections. ACS Infect. Dis. 6, 1615–1623. https://doi.org/10.1021/acsinfecdis.0c00050 (2020).
doi: 10.1021/acsinfecdis.0c00050 pubmed: 32329605 pmcid: 7354219
Shaper, M., Hollingshead, S. K., Benjamin, W. H. Jr. & Briles, D. E. PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin [corrected]. Infect. Immun. 72, 5031–5040. https://doi.org/10.1128/IAI.72.9.5031-5040.2004 (2004).
doi: 10.1128/IAI.72.9.5031-5040.2004 pubmed: 15321996 pmcid: 517438
Andre, G. O. et al. Combined effects of lactoferrin and lysozyme on Streptococcus pneumoniae killing. Microb. Pathog. 89, 7–17. https://doi.org/10.1016/j.micpath.2015.08.008 (2015).
doi: 10.1016/j.micpath.2015.08.008 pubmed: 26298002
Batista Araujo, J., de Souza, S., Lorenzon, E. N. & G. & Indolicidin revisited: biological activity, potential applications and perspectives of an antimicrobial peptide not yet fully explored. World J. Microbiol. Biotechnol. 38, 39. https://doi.org/10.1007/s11274-022-03227-2 (2022).
doi: 10.1007/s11274-022-03227-2 pubmed: 35018535
Ahmed, A. et al. Synthetic host defense peptides inhibit Venezuelan equine encephalitis virus replication and the Associated Inflammatory Response. Sci. Rep. 10, 21491. https://doi.org/10.1038/s41598-020-77990-3 (2020).
doi: 10.1038/s41598-020-77990-3 pubmed: 33293592 pmcid: 7722873
Nan, Y. H., Bang, J. K. & Shin, S. Y. Design of novel indolicidin-derived antimicrobial peptides with enhanced cell specificity and potent anti-inflammatory activity. Peptides. 30, 832–838. https://doi.org/10.1016/j.peptides.2009.01.015 (2009).
doi: 10.1016/j.peptides.2009.01.015 pubmed: 19428758
Smirnova, M. P. et al. Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity. Peptides. 132 https://doi.org/10.1016/j.peptides.2020.170356 (2020).
Vegh, A. G. et al. Effect of antimicrobial peptide-amide: Indolicidin on biological membranes. J. Biomed. Biotechnol. 2011 (670589). https://doi.org/10.1155/2011/670589 (2011).
Ebbensgaard, A. et al. Comparative evaluation of the antimicrobial activity of different antimicrobial peptides against a range of pathogenic Bacteria. PLoS One. 10, e0144611. https://doi.org/10.1371/journal.pone.0144611 (2015).
doi: 10.1371/journal.pone.0144611 pubmed: 26656394 pmcid: 4684357
Ghosh, A. et al. Indolicidin targets duplex DNA: Structural and mechanistic insight through a combination of spectroscopy and microscopy. ChemMedChem. 9, 2052–2058. https://doi.org/10.1002/cmdc.201402215 (2014).
doi: 10.1002/cmdc.201402215 pubmed: 25044630
Marchand, C. et al. Covalent binding of the natural antimicrobial peptide indolicidin to DNA abasic sites. Nucl. Acids Res. 34, 5157–5165. https://doi.org/10.1093/nar/gkl667 (2006).
doi: 10.1093/nar/gkl667 pubmed: 16998183 pmcid: 1636436
Rowe-Magnus, D. A., Kao, A. Y., Prieto, A. C., Pu, M. & Kao, C. Cathelicidin Peptides Restrict Bacterial Growth via Membrane Perturbation and Induction of Reactive Oxygen Species. mBio 10 https://doi.org/10.1128/mBio.02021-19 (2019).
Darrieux, M. et al. Recognition of pneumococcal isolates by antisera raised against PspA fragments from different clades. J. Med. Microbiol. 57, 273–278. https://doi.org/10.1099/jmm.0.47661-0 (2008).
doi: 10.1099/jmm.0.47661-0 pubmed: 18287288
Goulart, C. et al. Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells. Vaccine. 29, 1634–1642. https://doi.org/10.1016/j.vaccine.2010.12.074 (2011).
doi: 10.1016/j.vaccine.2010.12.074 pubmed: 21211592
Lane, J. R., Tata, M., Briles, D. E. & Orihuela, C. J. A Jack of all trades: the role of Pneumococcal surface protein A in the pathogenesis of Streptococcus pneumoniae. Front. Cell. Infect. Microbiol. 12, 826264. https://doi.org/10.3389/fcimb.2022.826264 (2022).
doi: 10.3389/fcimb.2022.826264 pubmed: 35186799 pmcid: 8847780
Mukerji, R. et al. Pneumococcal surface protein A inhibits complement deposition on the pneumococcal surface by competing with the binding of C-reactive protein to cell-surface phosphocholine. J. Immunol. 189, 5327–5335. https://doi.org/10.4049/jimmunol.1201967 (2012).
doi: 10.4049/jimmunol.1201967 pubmed: 23105137
Ren, B., Li, J., Genschmer, K., Hollingshead, S. K. & Briles, D. E. The absence of PspA or presence of antibody to PspA facilitates the complement-dependent phagocytosis of pneumococci in vitro. Clin. Vaccine Immunology: CVI. 19, 1574–1582. https://doi.org/10.1128/CVI.00393-12 (2012).
doi: 10.1128/CVI.00393-12 pubmed: 22855389 pmcid: 3485889
Park, S. S. et al. Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza. Cell. Rep. 35, 109267. https://doi.org/10.1016/j.celrep.2021.109267 (2021).
doi: 10.1016/j.celrep.2021.109267 pubmed: 34133917 pmcid: 8265312
Hollingshead, S. K., Becker, R. & Briles, D. E. Diversity of PspA: Mosaic genes and evidence for past recombination in Streptococcus pneumoniae. Infect. Immun. 68, 5889–5900. https://doi.org/10.1128/iai.68.10.5889-5900.2000 (2000).
doi: 10.1128/iai.68.10.5889-5900.2000 pubmed: 10992499 pmcid: 101551
Jindal, H. M. et al. Antimicrobial activity of Novel synthetic peptides derived from Indolicidin and Ranalexin against Streptococcus pneumoniae. PLoS One. 10, e0128532. https://doi.org/10.1371/journal.pone.0128532 (2015).
doi: 10.1371/journal.pone.0128532 pubmed: 26046345 pmcid: 4457802
Llobet, E., Tomas, J. M. & Bengoechea, J. A. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiol. (Reading). 154, 3877–3886. https://doi.org/10.1099/mic.0.2008/022301-0 (2008).
doi: 10.1099/mic.0.2008/022301-0
Waz, N. T. et al. Influence of the Polysaccharide Capsule on the bactericidal activity of Indolicidin on Streptococcus pneumoniae. Front. Microbiol. 13, 898815. https://doi.org/10.3389/fmicb.2022.898815 (2022).
doi: 10.3389/fmicb.2022.898815 pubmed: 35633685 pmcid: 9136410
Mirza, S. et al. The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin. Microb. Pathog. 99, 209–219. https://doi.org/10.1016/j.micpath.2016.08.029 (2016).
doi: 10.1016/j.micpath.2016.08.029 pubmed: 27569531
Senkovich, O. et al. Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism. J. Mol. Biol. 370, 701–713. https://doi.org/10.1016/j.jmb.2007.04.075 (2007).
doi: 10.1016/j.jmb.2007.04.075 pubmed: 17543335 pmcid: 5356469
Li, J., Glover, D. T., Szalai, A. J., Hollingshead, S. K. & Briles, D. E. PspA and PspC minimize immune adherence and transfer of pneumococci from erythrocytes to macrophages through their effects on complement activation. Infect. Immun. 75, 5877–5885. https://doi.org/10.1128/IAI.00839-07 (2007).
doi: 10.1128/IAI.00839-07 pubmed: 17923519 pmcid: 2168335
Aceil, J. & Avci, F. Y. Pneumococcal surface proteins as virulence factors, immunogens, and conserved vaccine targets. Front. Cell. Infect. Microbiol. 12, 832254. https://doi.org/10.3389/fcimb.2022.832254 (2022).
doi: 10.3389/fcimb.2022.832254 pubmed: 35646747 pmcid: 9133333
Avery, O. T., Macleod, C. M. & McCarty, M. Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal types: Induction of Transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus Type Iii. J. Exp. Med. 79, 137–158. https://doi.org/10.1084/jem.79.2.137 (1944).
doi: 10.1084/jem.79.2.137 pubmed: 19871359 pmcid: 2135445
Roche, H., Hakansson, A., Hollingshead, S. K. & Briles, D. E. Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model. Infect. Immun. 71, 1033–1041 (2003).
doi: 10.1128/IAI.71.3.1033-1041.2003 pubmed: 12595413 pmcid: 148823
Magee, A. D. & Yother, J. Requirement for capsule in colonization by Streptococcus pneumoniae. Infect. Immun. 69, 3755–3761. https://doi.org/10.1128/IAI.69.6.3755-3761.2001 (2001).
doi: 10.1128/IAI.69.6.3755-3761.2001 pubmed: 11349040 pmcid: 98386
Tettelin, H. et al. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science. 293, 498–506. https://doi.org/10.1126/science.1061217 (2001).
doi: 10.1126/science.1061217 pubmed: 11463916
Cuppone, A. M. et al. Complete genome sequence of Streptococcus pneumoniae strain Rx1, a Hex Mismatch Repair-Deficient Standard Transformation recipient. Microbiol. Resour. Announc. 10, e0079921. https://doi.org/10.1128/MRA.00799-21 (2021).
doi: 10.1128/MRA.00799-21 pubmed: 34647809
Shoemaker, N. B. & Guild, W. R. Destruction of low efficiency markers is a slow process occurring at a heteroduplex stage of transformation. Mol. Gen. Genet. 128, 283–290. https://doi.org/10.1007/BF00268516 (1974).
doi: 10.1007/BF00268516 pubmed: 4150368
Brooks-Walter, A., Briles, D. E. & Hollingshead, S. K. The pspC gene of Streptococcus pneumoniae encodes a polymorphic protein, PspC, which elicits cross-reactive antibodies to PspA and provides immunity to pneumococcal bacteremia. Infect. Immun. 67, 6533–6542 (1999).
doi: 10.1128/IAI.67.12.6533-6542.1999 pubmed: 10569772 pmcid: 97064
Liu, S., McClure, T. R., Styba, S., Shi, G. & Jackowski, Q. Removal of Endotoxin from recombinant protein preparations. Clin. Biochem. 30 https://doi.org/10.1016/S0009-9120(97)00049-0 (1997).

Auteurs

Natalha T Waz (NT)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Barbara Milani (B)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Lucas Assoni (L)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Guilherme Rabelo Coelho (GR)

Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, Brazil.

Juliana M Sciani (JM)

Laboratório de Produtos Naturais, Universidade São Francisco, Bragança Paulista, Brazil.

Thaís Parisotto (T)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Lucio F C Ferraz (LFC)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Anders P Hakansson (AP)

Division of Experimental Infection Medicine, Department of Translational Medicine, Lund University, Lund, Sweden.

Thiago R Converso (TR)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil.

Michelle Darrieux (M)

Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, Brazil. michelle.bertoncini@usf.edu.br.

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