Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria

Autores
Martínez Júlvez, Marta; Goñi Rasia, Guillermina Marcela; Pérez Amigot, Daniel; Laplaza, Rubén; Ionescu, Irina Alexandra; Petrocelli, Silvana; Tondo, Maria Laura; Sancho, Javier; Orellano, Elena Graciela; Medina, Milagros
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ferredoxin-NADP(H) reductases (FNRs) deliver NADPH or low potential one-electron donors to redox-based metabolism in plastids and bacteria. Xanthomonas citri subsp. citri (Xcc) is a Gram-negative bacterium responsible for citrus canker disease that affects commercial citrus crops worldwide. The Xcc fpr gene encodes a bacterial type FNR (XccFPR) that contributes to the bacterial response to oxidative stress conditions, usually found during plant colonization. Therefore, XccFPR is relevant for the pathogen survival and its inhibition might represent a strategy to treat citrus canker. Because of mechanistic and structural differences from plastidic FNRs, XccFPR is also a potential antibacterial target. We have optimized an activity-based high-throughput screening (HTS) assay that identifies XccFPR inhibitors. We selected 43 hits from a chemical library and narrowed them down to the four most promising inhibitors. The antimicrobial effect of these compounds was evaluated on Xcc cultures, finding one with antimicrobial properties. Based on the functional groups of this compound and their geometric arrangement, we identified another three XccFPR inhibitors. Inhibition mechanisms and constants were determined for these four XccFPR inhibitors. Their specificity was also evaluated by studying their effect on the plastidic Anabaena PCC 7119 FNR, finding differences that can become interesting tools to discover Xcc antimicrobials.
Fil: Martínez Júlvez, Marta. Universidad de Zaragoza; España
Fil: Goñi Rasia, Guillermina Marcela. Universidad de Zaragoza; España
Fil: Pérez Amigot, Daniel. Universidad de Zaragoza; España
Fil: Laplaza, Rubén. Universidad de Zaragoza; España. Universidad de Santiago de Compostela; España
Fil: Ionescu, Irina Alexandra. Universidad de Zaragoza; España
Fil: Petrocelli, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Tondo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Sancho, Javier. Universidad de Zaragoza; España
Fil: Orellano, Elena Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Medina, Milagros. Universidad de Zaragoza; España
Materia
ACTIVITY-BASED HIGH-THROUGHPUT SCREENING
ENZYME INHIBITORS
FERREDOXIN-NADP(H) REDUCTASE
XANTHOMONAS CITRI SUBSP. CITRI
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:11336/53227
Acceder
id CONICETDig_afcd2491b5b1f35fff9ee5f9f5603537
oai_identifier_str oai:ri.conicet.gov.ar:11336/53227
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteriaMartínez Júlvez, MartaGoñi Rasia, Guillermina MarcelaPérez Amigot, DanielLaplaza, RubénIonescu, Irina AlexandraPetrocelli, SilvanaTondo, Maria LauraSancho, JavierOrellano, Elena GracielaMedina, MilagrosACTIVITY-BASED HIGH-THROUGHPUT SCREENINGENZYME INHIBITORSFERREDOXIN-NADP(H) REDUCTASEXANTHOMONAS CITRI SUBSP. CITRIhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Ferredoxin-NADP(H) reductases (FNRs) deliver NADPH or low potential one-electron donors to redox-based metabolism in plastids and bacteria. Xanthomonas citri subsp. citri (Xcc) is a Gram-negative bacterium responsible for citrus canker disease that affects commercial citrus crops worldwide. The Xcc fpr gene encodes a bacterial type FNR (XccFPR) that contributes to the bacterial response to oxidative stress conditions, usually found during plant colonization. Therefore, XccFPR is relevant for the pathogen survival and its inhibition might represent a strategy to treat citrus canker. Because of mechanistic and structural differences from plastidic FNRs, XccFPR is also a potential antibacterial target. We have optimized an activity-based high-throughput screening (HTS) assay that identifies XccFPR inhibitors. We selected 43 hits from a chemical library and narrowed them down to the four most promising inhibitors. The antimicrobial effect of these compounds was evaluated on Xcc cultures, finding one with antimicrobial properties. Based on the functional groups of this compound and their geometric arrangement, we identified another three XccFPR inhibitors. Inhibition mechanisms and constants were determined for these four XccFPR inhibitors. Their specificity was also evaluated by studying their effect on the plastidic Anabaena PCC 7119 FNR, finding differences that can become interesting tools to discover Xcc antimicrobials.Fil: Martínez Júlvez, Marta. Universidad de Zaragoza; EspañaFil: Goñi Rasia, Guillermina Marcela. Universidad de Zaragoza; EspañaFil: Pérez Amigot, Daniel. Universidad de Zaragoza; EspañaFil: Laplaza, Rubén. Universidad de Zaragoza; España. Universidad de Santiago de Compostela; EspañaFil: Ionescu, Irina Alexandra. Universidad de Zaragoza; EspañaFil: Petrocelli, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Tondo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Sancho, Javier. Universidad de Zaragoza; EspañaFil: Orellano, Elena Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Medina, Milagros. Universidad de Zaragoza; EspañaMolecular Diversity Preservation International2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53227Martínez Júlvez, Marta; Goñi Rasia, Guillermina Marcela; Pérez Amigot, Daniel; Laplaza, Rubén; Ionescu, Irina Alexandra; et al.; Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria; Molecular Diversity Preservation International; Molecules; 23; 1; 12-2017; 1-151420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23010029info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/1/29info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:51Zoai:ri.conicet.gov.ar:11336/53227instacron: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 10:02:51.331CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
title Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
spellingShingle Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
Martínez Júlvez, Marta
ACTIVITY-BASED HIGH-THROUGHPUT SCREENING
ENZYME INHIBITORS
FERREDOXIN-NADP(H) REDUCTASE
XANTHOMONAS CITRI SUBSP. CITRI
title_short Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
title_full Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
title_fullStr Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
title_full_unstemmed Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
title_sort Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria
dc.creator.none.fl_str_mv Martínez Júlvez, Marta
Goñi Rasia, Guillermina Marcela
Pérez Amigot, Daniel
Laplaza, Rubén
Ionescu, Irina Alexandra
Petrocelli, Silvana
Tondo, Maria Laura
Sancho, Javier
Orellano, Elena Graciela
Medina, Milagros
author Martínez Júlvez, Marta
author_facet Martínez Júlvez, Marta
Goñi Rasia, Guillermina Marcela
Pérez Amigot, Daniel
Laplaza, Rubén
Ionescu, Irina Alexandra
Petrocelli, Silvana
Tondo, Maria Laura
Sancho, Javier
Orellano, Elena Graciela
Medina, Milagros
author_role author
author2 Goñi Rasia, Guillermina Marcela
Pérez Amigot, Daniel
Laplaza, Rubén
Ionescu, Irina Alexandra
Petrocelli, Silvana
Tondo, Maria Laura
Sancho, Javier
Orellano, Elena Graciela
Medina, Milagros
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVITY-BASED HIGH-THROUGHPUT SCREENING
ENZYME INHIBITORS
FERREDOXIN-NADP(H) REDUCTASE
XANTHOMONAS CITRI SUBSP. CITRI
topic ACTIVITY-BASED HIGH-THROUGHPUT SCREENING
ENZYME INHIBITORS
FERREDOXIN-NADP(H) REDUCTASE
XANTHOMONAS CITRI SUBSP. CITRI
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Ferredoxin-NADP(H) reductases (FNRs) deliver NADPH or low potential one-electron donors to redox-based metabolism in plastids and bacteria. Xanthomonas citri subsp. citri (Xcc) is a Gram-negative bacterium responsible for citrus canker disease that affects commercial citrus crops worldwide. The Xcc fpr gene encodes a bacterial type FNR (XccFPR) that contributes to the bacterial response to oxidative stress conditions, usually found during plant colonization. Therefore, XccFPR is relevant for the pathogen survival and its inhibition might represent a strategy to treat citrus canker. Because of mechanistic and structural differences from plastidic FNRs, XccFPR is also a potential antibacterial target. We have optimized an activity-based high-throughput screening (HTS) assay that identifies XccFPR inhibitors. We selected 43 hits from a chemical library and narrowed them down to the four most promising inhibitors. The antimicrobial effect of these compounds was evaluated on Xcc cultures, finding one with antimicrobial properties. Based on the functional groups of this compound and their geometric arrangement, we identified another three XccFPR inhibitors. Inhibition mechanisms and constants were determined for these four XccFPR inhibitors. Their specificity was also evaluated by studying their effect on the plastidic Anabaena PCC 7119 FNR, finding differences that can become interesting tools to discover Xcc antimicrobials.
Fil: Martínez Júlvez, Marta. Universidad de Zaragoza; España
Fil: Goñi Rasia, Guillermina Marcela. Universidad de Zaragoza; España
Fil: Pérez Amigot, Daniel. Universidad de Zaragoza; España
Fil: Laplaza, Rubén. Universidad de Zaragoza; España. Universidad de Santiago de Compostela; España
Fil: Ionescu, Irina Alexandra. Universidad de Zaragoza; España
Fil: Petrocelli, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Tondo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Sancho, Javier. Universidad de Zaragoza; España
Fil: Orellano, Elena Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Medina, Milagros. Universidad de Zaragoza; España
description Ferredoxin-NADP(H) reductases (FNRs) deliver NADPH or low potential one-electron donors to redox-based metabolism in plastids and bacteria. Xanthomonas citri subsp. citri (Xcc) is a Gram-negative bacterium responsible for citrus canker disease that affects commercial citrus crops worldwide. The Xcc fpr gene encodes a bacterial type FNR (XccFPR) that contributes to the bacterial response to oxidative stress conditions, usually found during plant colonization. Therefore, XccFPR is relevant for the pathogen survival and its inhibition might represent a strategy to treat citrus canker. Because of mechanistic and structural differences from plastidic FNRs, XccFPR is also a potential antibacterial target. We have optimized an activity-based high-throughput screening (HTS) assay that identifies XccFPR inhibitors. We selected 43 hits from a chemical library and narrowed them down to the four most promising inhibitors. The antimicrobial effect of these compounds was evaluated on Xcc cultures, finding one with antimicrobial properties. Based on the functional groups of this compound and their geometric arrangement, we identified another three XccFPR inhibitors. Inhibition mechanisms and constants were determined for these four XccFPR inhibitors. Their specificity was also evaluated by studying their effect on the plastidic Anabaena PCC 7119 FNR, finding differences that can become interesting tools to discover Xcc antimicrobials.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
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/11336/53227
Martínez Júlvez, Marta; Goñi Rasia, Guillermina Marcela; Pérez Amigot, Daniel; Laplaza, Rubén; Ionescu, Irina Alexandra; et al.; Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria; Molecular Diversity Preservation International; Molecules; 23; 1; 12-2017; 1-15
1420-3049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53227
identifier_str_mv Martínez Júlvez, Marta; Goñi Rasia, Guillermina Marcela; Pérez Amigot, Daniel; Laplaza, Rubén; Ionescu, Irina Alexandra; et al.; Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria; Molecular Diversity Preservation International; Molecules; 23; 1; 12-2017; 1-15
1420-3049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23010029
info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/1/29
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
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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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