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 X...

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Autores principales: 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
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: MDPI 2021
Materias:
Activity-Based High-Throughput Screening;
Enzyme Inhibitors
Ferredoxin-NADP Reductase
Xanthomonas citri subsp. citri
Acceso en línea:http://hdl.handle.net/2133/19666
http://hdl.handle.net/2133/19666
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-19666
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Activity-Based High-Throughput Screening;
Enzyme Inhibitors
Ferredoxin-NADP Reductase
Xanthomonas citri subsp. citri
spellingShingle Activity-Based High-Throughput Screening;
Enzyme Inhibitors
Ferredoxin-NADP Reductase
Xanthomonas citri subsp. citri
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
topic_facet Activity-Based High-Throughput Screening;
Enzyme Inhibitors
Ferredoxin-NADP Reductase
Xanthomonas citri subsp. citri
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 article
artículo
publishedVersion
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
title 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_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
publisher MDPI
publishDate 2021
url http://hdl.handle.net/2133/19666
http://hdl.handle.net/2133/19666
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