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Identification of Inhibitors Targeting Ferredoxin-NADP(+) Reductase from the Xanthomonas citri subsp. citri Phytopathogenic Bacteria
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943930/ https://www.ncbi.nlm.nih.gov/pubmed/29295539 http://dx.doi.org/10.3390/molecules23010029 |
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author | Martínez-Júlvez, Marta Goñi, Guillermina Pérez-Amigot, Daniel Laplaza, Rubén Ionescu, Irina Alexandra Petrocelli, Silvana Tondo, María Laura Sancho, Javier Orellano, Elena G. Medina, Milagros |
author_facet | Martínez-Júlvez, Marta Goñi, Guillermina Pérez-Amigot, Daniel Laplaza, Rubén Ionescu, Irina Alexandra Petrocelli, Silvana Tondo, María Laura Sancho, Javier Orellano, Elena G. Medina, Milagros |
author_sort | Martínez-Júlvez, Marta |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-5943930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59439302018-11-13 Identification of Inhibitors Targeting Ferredoxin-NADP(+) Reductase from the Xanthomonas citri subsp. citri Phytopathogenic Bacteria Martínez-Júlvez, Marta Goñi, Guillermina Pérez-Amigot, Daniel Laplaza, Rubén Ionescu, Irina Alexandra Petrocelli, Silvana Tondo, María Laura Sancho, Javier Orellano, Elena G. Medina, Milagros Molecules Article 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. MDPI 2017-12-24 /pmc/articles/PMC5943930/ /pubmed/29295539 http://dx.doi.org/10.3390/molecules23010029 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Martínez-Júlvez, Marta Goñi, Guillermina Pérez-Amigot, Daniel Laplaza, Rubén Ionescu, Irina Alexandra Petrocelli, Silvana Tondo, María Laura Sancho, Javier Orellano, Elena G. Medina, Milagros 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 |
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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943930/ https://www.ncbi.nlm.nih.gov/pubmed/29295539 http://dx.doi.org/10.3390/molecules23010029 |
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