Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides

Autores
Lopez Garcia, Belén; Harries, Eleonora del Milagro; Carmona, Lourdes; Campos Soriano, Lidia; López, José Javier; Manzanares, Paloma; Gandía, Mónica; Coca, María; Marcos, Jose F.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.
Fil: Lopez Garcia, Belén. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: Harries, Eleonora del Milagro. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta; Argentina
Fil: Carmona, Lourdes. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Campos Soriano, Lidia. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: López, José Javier. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Manzanares, Paloma. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Gandía, Mónica. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Coca, María. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: Marcos, Jose F.. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Materia
Antifungal
Peptide
Penicillium
Fusarium
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7106
Acceder
id CONICETDig_d2991061d67855e25af36871e2559488
oai_identifier_str oai:ri.conicet.gov.ar:11336/7106
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptidesLopez Garcia, BelénHarries, Eleonora del MilagroCarmona, LourdesCampos Soriano, LidiaLópez, José JavierManzanares, PalomaGandía, MónicaCoca, MaríaMarcos, Jose F.AntifungalPeptidePenicilliumFusariumhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.Fil: Lopez Garcia, Belén. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; EspañaFil: Harries, Eleonora del Milagro. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta; ArgentinaFil: Carmona, Lourdes. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; EspañaFil: Campos Soriano, Lidia. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; EspañaFil: López, José Javier. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; EspañaFil: Manzanares, Paloma. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; EspañaFil: Gandía, Mónica. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; EspañaFil: Coca, María. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; EspañaFil: Marcos, Jose F.. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; EspañaSpringer2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7106Lopez Garcia, Belén; Harries, Eleonora del Milagro; Carmona, Lourdes; Campos Soriano, Lidia; López, José Javier; et al.; Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides; Springer; Applied Microbiology And Biotechnology; 99; 19; 4-2015; 8011-80210175-7598enginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007/s00253-015-6541-1info:eu-repo/semantics/altIdentifier/doi/10.1007/s00253-015-6541-1info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:31Zoai:ri.conicet.gov.ar:11336/7106instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:45:31.899CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
title Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
spellingShingle Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
Lopez Garcia, Belén
Antifungal
Peptide
Penicillium
Fusarium
title_short Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
title_full Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
title_fullStr Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
title_full_unstemmed Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
title_sort Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides
dc.creator.none.fl_str_mv Lopez Garcia, Belén
Harries, Eleonora del Milagro
Carmona, Lourdes
Campos Soriano, Lidia
López, José Javier
Manzanares, Paloma
Gandía, Mónica
Coca, María
Marcos, Jose F.
author Lopez Garcia, Belén
author_facet Lopez Garcia, Belén
Harries, Eleonora del Milagro
Carmona, Lourdes
Campos Soriano, Lidia
López, José Javier
Manzanares, Paloma
Gandía, Mónica
Coca, María
Marcos, Jose F.
author_role author
author2 Harries, Eleonora del Milagro
Carmona, Lourdes
Campos Soriano, Lidia
López, José Javier
Manzanares, Paloma
Gandía, Mónica
Coca, María
Marcos, Jose F.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antifungal
Peptide
Penicillium
Fusarium
topic Antifungal
Peptide
Penicillium
Fusarium
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.
Fil: Lopez Garcia, Belén. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: Harries, Eleonora del Milagro. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta; Argentina
Fil: Carmona, Lourdes. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Campos Soriano, Lidia. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: López, José Javier. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Manzanares, Paloma. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Gandía, Mónica. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
Fil: Coca, María. Consejo Superior de Investigaciones Cientificas. Centre for Research in Agricultural Genomics; España
Fil: Marcos, Jose F.. Consejo Superior de Investigaciones Cientificas. Instituto de Agroquimica y Tecnologia de Alimentos; España
description There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7106
Lopez Garcia, Belén; Harries, Eleonora del Milagro; Carmona, Lourdes; Campos Soriano, Lidia; López, José Javier; et al.; Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides; Springer; Applied Microbiology And Biotechnology; 99; 19; 4-2015; 8011-8021
0175-7598
url http://hdl.handle.net/11336/7106
identifier_str_mv Lopez Garcia, Belén; Harries, Eleonora del Milagro; Carmona, Lourdes; Campos Soriano, Lidia; López, José Javier; et al.; Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides; Springer; Applied Microbiology And Biotechnology; 99; 19; 4-2015; 8011-8021
0175-7598
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007/s00253-015-6541-1
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00253-015-6541-1
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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