{"id":132166,"date":"2026-02-20T11:16:55","date_gmt":"2026-02-20T10:16:55","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/new-insights-into-how-bacteria-control-dna-synthesis-open-the-door-to-next%e2%80%91generation-antimicrobials\/"},"modified":"2026-02-20T12:52:37","modified_gmt":"2026-02-20T11:52:37","slug":"new-insights-into-how-bacteria-control-dna-synthesis-open-the-door-to-next%e2%80%91generation-antimicrobials","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/un-nou-estudi-sobre-la-sintesi-adn-en-bacteris-impulsa-la-recerca-de-la-proxima-generacio-antibiotics","title":{"rendered":"Un nou estudi sobre la s\u00edntesi d’ADN en bacteris impulsa la recerca de la pr\u00f2xima generaci\u00f3 d’antibi\u00f2tics"},"content":{"rendered":"\n

Un estudi dirigit per l’Institut de Bioenginyeria de Catalunya (IBEC) i l’Institut de Biologia Molecular de Barcelona (IBMB) ofereix la imatge m\u00e9s detallada fins a la data de l\u2019NrdR, el regulador principal dels ribonucle\u00f2tids (RNR) en els bacteris. Els investigadors van obtenir les primeres imatges detallades de l’estructura completa de la prote\u00efna l\u2019NrdR i van demostrar com els canvis en la forma i l’associaci\u00f3 d’aquesta prote\u00efna afecten la manera en qu\u00e8 controla processos clau dins de la c\u00e8l\u00b7lula. Les troballes, publicades recentment a la revista International Journal of Biological Macromolecules<\/em>, amplien la nostra comprensi\u00f3 de com els bacteris regulen la producci\u00f3 dels components moleculars de l’ADN, un aspecte crucial tant per a la microbiologia fonamental com per al desenvolupament de noves estrat\u00e8gies antimicrobianes.<\/strong><\/strong><\/a><\/p>\n\n\n\n

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Maria Sol\u00e0 (esquerra) i Eduard Torrents (dreta).<\/figcaption><\/figure>\n\n\n\n

Els ribonucle\u00f2tids (RNR) s\u00f3n enzims indispensables que converteixen els ribonucle\u00f2tids en desoxirribonucle\u00f2tids (dNTP), els precursors que componen l’ADN. At\u00e8s que la s\u00edntesi de l’ADN \u00e9s fonamental per a la superviv\u00e8ncia cel\u00b7lular, l’activitat de les RNR s’ha de controlar de manera molt estricta. En els bacteris, aquest control l’exerceix un regulador transcripcional especialitzat, l\u2019NrdR, que no t\u00e9 equivalent en els organismes eucariotes i, per tant, representa una diana potencial per al desenvolupament d’antimicrobians. Malgrat el seu paper central, la base estructural de la funci\u00f3 de l\u2019NrdR i els mecanismes pels quals detecta els nivells de nucle\u00f2tids cel\u00b7lulars i modula l’expressi\u00f3 dels RNR nom\u00e9s es coneixien parcialment fins al moment.<\/p>\n\n\n\n

Ara, aquest estudi aborda aquesta llacuna combinant la biologia estructural, la caracteritzaci\u00f3 biof\u00edsica i els assajos funcionals per dibuixar com l’estructura quatern\u00e0ria de l\u2019NrdR respon a diferents estats de nucle\u00f2tids i com aquests canvis afecten la seva activitat reguladora. Els investigadors van centrar el seu estudi en dos importants pat\u00f2gens bacterians: Escherichia coli<\/em>, un patogen model clau per a l’estudi de la fisiologia bacteriana fonamental, i Pseudomonas aeruginosa<\/em>, un patogen oportunista reconegut per la seva resist\u00e8ncia inherent a molts antibi\u00f2tics i el seu paper en les infeccions cr\u00f2niques. El treball de recerca va ser dirigit pel grup Infeccions Bacterianes: Ter\u00e0pies Antimicrobianes<\/a>, de l’Institut de Bioenginyeria de Catalunya (IBEC) i el grup de Biologia Estructural de Macromol\u00e8cules Mitocondrials<\/a> de l’Institut de Biologia Molecular de Barcelona (IBMB-CSIC), amb la participaci\u00f3 del grup de Caracteritzaci\u00f3 Bioel\u00e8ctrica a la Nanoescala<\/a> de  l’IBEC.<\/p>\n\n\n\n

L\u2019NrdR com a possible nova diana contra les infeccions bacterianes<\/strong><\/strong><\/h4>\n\n\n\n
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Apuntar a un regulador tan important podria debilitar els bacteris pat\u00f2gens o ajudar a restaurar la seva susceptibilitat als antibi\u00f2tics existents, cosa que representa una via prometedora per contrarestar la creixent resist\u00e8ncia als antimicrobians.<\/p>\n\n\n\n

Eduard Torrents<\/p>\n<\/blockquote>\n\n\n\n

La caracteritzaci\u00f3 exhaustiva de l’estructura i el mecanisme de NrdR suposa un aven\u00e7 significatiu en la nostra comprensi\u00f3 de la regulaci\u00f3 transcripcional bacteriana. En revelar com els bacteris regulen la s\u00edntesi de desoxiribonucle\u00f2tids en resposta a les fluctuacions de nucle\u00f2tids, aquest treball proporciona una base conceptual i experimental per a la identificaci\u00f3 de nous objectius antibacterians i la innovaci\u00f3 terap\u00e8utica futura.<\/p>\n\n\n\n

Entendre com l\u2019NrdR detecta els nivells de nucle\u00f2tids i controla l’expressi\u00f3 de gens RNR essencials proporciona un nou punt de partida estrat\u00e8gic per al desenvolupament d’antimicrobians. At\u00e8s que NrdR est\u00e0 absent en les c\u00e8l\u00b7lules humanes i exerceix un paper fonamental en la s\u00edntesi de precursors de l’ADN bacteri\u00e0, els coneixements estructurals descoberts aqu\u00ed ofereixen una base s\u00f2lida per dissenyar mol\u00e8cules que alterin selectivament l’home\u00f2stasi dels nucle\u00f2tids bacterians. Aquests coneixements posicionen NrdR com una diana antimicrobiana molt interessant la manipulaci\u00f3 de la qual pot inspirar estrat\u00e8gies de pr\u00f2xima generaci\u00f3 per combatre les infeccions bacterianes resistents.<\/p>\n\n\n\n

\u00abApuntar a un regulador tan important podria debilitar els bacteris pat\u00f2gens o ajudar a restaurar la seva susceptibilitat als antibi\u00f2tics existents, cosa que representa una via prometedora per contrarestar la creixent resist\u00e8ncia als antimicrobians\u00bb, explica Eduard Torrents, investigador principal del grup Infeccions Bacterianes: ter\u00e0pies antimicrobianes de l’IBEC, professor associat de la Universitat de Barcelona (UB),  membre d’ICREA Acad\u00e8mia i autor de l’estudi.<\/p>\n\n\n\n

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Estructura de l’NrdR cristal\u00b7litzat<\/figcaption><\/figure><\/div><\/div>\n\n\n\n
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Representaci\u00f3 esquem\u00e0tica de l’NrdR<\/figcaption><\/figure><\/div><\/div>\n<\/div>\n\n\n\n

Desxifrant l’estructura 3D de l\u2019NrdR i la seva import\u00e0ncia biol\u00f2gica<\/strong><\/strong><\/h4>\n\n\n\n

Els investigadors van identificar primer quins gens estan controlats per l\u2019NrdR en aquests bacteris integrant dades transcript\u00f2miques amb an\u00e0lisi de motius, cosa que va proporcionar una imatge m\u00e9s clara de com aquest regulador influeix en els processos cel\u00b7lulars essencials. A continuaci\u00f3, l’equip va determinar, mitjan\u00e7ant cristal\u00b7lografia de prote\u00efnes amb raigs X, l’estructura tridimensional de la prote\u00efna l\u2019NrdR a E. coli<\/em>, descobrint com les mol\u00e8cules de prote\u00efna s’associen entre si per formar assemblatges. Tot i que van utilitzar diferents t\u00e8cniques, com la dispersi\u00f3 de llum multiangle (SEC-MALS) i la microsc\u00f2pia de for\u00e7a at\u00f2mica, els investigadors tamb\u00e9 van examinar com aquests assemblatges canvien en resposta a la pres\u00e8ncia de diferents nucle\u00f2tids, revelant un sistema altament din\u00e0mic regulat per aquests metab\u00f2lits. \u00abDespr\u00e9s de determinar l’estructura cristal\u00b7lina, el seg\u00fcent pas crucial \u00e9s desxifrar si les interaccions observades en el vidre tenen significat biol\u00f2gic, en aquest cas, com l\u2019NrdR respon als nucle\u00f2tids\u00bb, afirma Maria Sol\u00e0, investigadora principal del grup de Biologia Estructural de Macromol\u00e8cules Mitocondrials de l’Institut de Biologia Molecular de Barcelona (IBMB-CSIC) i autora de l’estudi. <\/p>\n\n\n\n

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Despr\u00e9s de determinar l’estructura cristal\u00b7lina, el seg\u00fcent pas crucial \u00e9s desxifrar si les interaccions observades en el vidre tenen significat biol\u00f2gic, en aquest cas, com l\u2019NrdR respon als nucle\u00f2tids.<\/p>\n\n\n\n

Maria Sol\u00e0<\/p>\n<\/blockquote>\n\n\n\n

Per abordar l’impacte dels estats estructurals en l’activitat d’uni\u00f3 a l’ADN i la regulaci\u00f3, els investigadors van realitzar una validaci\u00f3 funcional de les interaccions prote\u00efna-prote\u00efna observades en el cristall utilitzant mutacions puntuals, assajos de despla\u00e7ament de mobilitat electrofor\u00e8tica i assajos de transcripci\u00f3 in vitro<\/em>. \u00c9s important destacar que el treball aclareix com l\u2019NrdR respon als senyals intracel\u00b7lulars \u2014en particular, ATP i dATP\u2014 per canviar entre estats actius i repressius, ajustant aix\u00ed l’expressi\u00f3 de RNR d’acord amb les necessitats cel\u00b7lulars<\/em>, explica Lucas Pedraz, co-primer autor de l’estudi. Aquestes troballes s’oposen a les visions anteriors, m\u00e9s simplistes, de la regulaci\u00f3 de l\u2019NrdR, i revelen un mecanisme finament ajustat pel qual la uni\u00f3 de nucle\u00f2tids impulsa transicions estructurals que influeixen directament en la uni\u00f3 a l’ADN i la repressi\u00f3 g\u00e8nica.<\/p>\n\n\n\n

En conjunt, aquests resultats posicionen l\u2019NrdR com una nova diana prometedora en la lluita contra la resist\u00e8ncia als antimicrobians, ja que ofereix una oportunitat \u00fanica per interrompre una via reguladora essencial per a la superviv\u00e8ncia dels bacteris, absent en els \u00e9ssers humans. En definir l’estructura de l\u2019NrdR i revelar com governa l\u2019home\u00f2stasi dels nucle\u00f2tids, aquest treball no nom\u00e9s aprofundeix la nostra comprensi\u00f3 de la biologia bacteriana, sin\u00f3 que tamb\u00e9 estableixi una base s\u00f2lida per al desenvolupament de ter\u00e0pies de pr\u00f2xima generaci\u00f3. A mesura que la resist\u00e8ncia als antibi\u00f2tics continua augmentant a tot el m\u00f3n, aquests coneixements proporcionen un trampol\u00ed crucial per a estrat\u00e8gies innovadores que debilitin els bacteris pat\u00f2gens i restaurin l’efic\u00e0cia dels tractaments existents.<\/p>\n\n\n\n

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Article de refer\u00e8ncia<\/strong><\/p>\n\n\n\n

Lucas Pedraz, Arkadiusz Szura, Claus Schmitz, Alba Rubio-Canalejas, \u00c1ngela Mart\u00ednez-Mateos, Anthony Santella, Gabriel Gomila, Annalisa Calo, Maria Sol\u00e0, Eduard Torrents. Structure and mechanistic basis of NrdR, a bacterial master regulator of ribonucleotide reduction.<\/strong> International Journal of Biological Macromolecules<\/em> (2026). DOI: https:\/\/doi.org\/10.1016\/j.ijbiomac.2026.150647<\/a><\/p>\n\n\n\n

\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Un estudi dirigit per l’Institut de Bioenginyeria de Catalunya (IBEC) i l’Institut de Biologia Molecular de Barcelona (IBMB) ofereix la imatge m\u00e9s detallada fins a la data de l\u2019NrdR, el regulador principal dels ribonucle\u00f2tids (RNR) en els bacteris. Els investigadors van obtenir les primeres imatges detallades de l’estructura completa de la prote\u00efna l\u2019NrdR i van demostrar com els canvis en la forma i l’associaci\u00f3 d’aquesta prote\u00efna afecten la manera en qu\u00e8 controla processos clau dins de la c\u00e8l\u00b7lula. Les troballes, publicades recentment a la revista International Journal of Biological Macromolecules, amplien la nostra comprensi\u00f3 de com els bacteris regulen la producci\u00f3 dels components moleculars de l’ADN, un aspecte crucial tant per a la microbiologia fonamental com per al desenvolupament de noves estrat\u00e8gies antimicrobianes.<\/p>\n","protected":false},"author":37,"featured_media":132150,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1905,1141,1114,1809],"post_formats":[],"class_list":["post-132166","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-bacterial-infections-and-antimicrobial-therapies-ca-2","tag-eduard-torrents-ca","tag-gabriel-gomila-ca","tag-nanoscale-bioelectrical-characterization-ca"],"yoast_head":"\nUn nou estudi sobre la s\u00edntesi d'ADN en bacteris impulsa la recerca de la pr\u00f2xima generaci\u00f3 d'antibi\u00f2tics - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/ca\/un-nou-estudi-sobre-la-sintesi-adn-en-bacteris-impulsa-la-recerca-de-la-proxima-generacio-antibiotics\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Un nou estudi sobre la s\u00edntesi d'ADN en bacteris impulsa la recerca de la pr\u00f2xima generaci\u00f3 d'antibi\u00f2tics - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Un estudi dirigit per l'Institut de Bioenginyeria de Catalunya (IBEC) i l'Institut de Biologia Molecular de Barcelona (IBMB) ofereix la imatge m\u00e9s detallada fins a la data de l\u2019NrdR, el regulador principal dels ribonucle\u00f2tids (RNR) en els bacteris. 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