000130077 001__ 130077
000130077 005__ 20240122171020.0
000130077 0247_ $$2doi$$a10.3390/ijms221810137
000130077 0248_ $$2sideral$$a125805
000130077 037__ $$aART-2021-125805
000130077 041__ $$aeng
000130077 100__ $$0(orcid)0000-0003-0195-5434$$aSalillas S.$$uUniversidad de Zaragoza
000130077 245__ $$aSelective targeting of human and animal pathogens of the helicobacter genus by flavodoxin inhibitors: Efficacy, synergy, resistance and mechanistic studies
000130077 260__ $$c2021
000130077 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130077 5203_ $$aAntimicrobial resistant (AMR) bacteria constitute a global health concern. Helicobacter py-lori is a Gram-negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple H. pylori eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting H. pylori. Here, we describe the antimicrobial spectrum of a family of nitrobenzoxadiazol-based antimicrobials initially discovered as inhibitors of flavodoxin: an essential H. pylori protein. Two groups of inhibitors are described. One group is formed by nar-row-spectrum compounds, highly specific for H. pylori, but ineffective against enterohepatic Helico-bacter species and other Gram-negative or Gram-positive bacteria. The second group includes ex-tended-spectrum antimicrobials additionally targeting Gram-positive bacteria, the Gram-negative Campylobacter jejuni, and most Helicobacter species, but not affecting other Gram-negative pathogens. To identify the binding site of the inhibitors in the flavodoxin structure, several H. pylori-flavodoxin variants have been engineered and tested using isothermal titration calorimetry. An initial study of the inhibitors capacity to generate resistances and of their synergism with antimicrobials commonly used in H. pylori eradication therapies is described. The narrow-spectrum inhibitors, which are ex-pected to affect the microbiota less dramatically than current antimicrobial drugs, offer an oppor-tunity to develop new and specific H. pylori eradication combinations to deal with AMR in H. pylori. On the other hand, the extended-spectrum inhibitors constitute a new family of promising antimi-crobials, with a potential use against AMR Gram-positive bacterial pathogens. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
000130077 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/DGA/LMP30-18$$9info:eu-repo/grantAgreement/EC/H2020/801586/EU/International Doctoral Programme for Talent Attraction to the Campus of International Excellence of the Ebro Valley/IberusTalent$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 801586-IberusTalent$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00
000130077 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000130077 590__ $$a6.208$$b2021
000130077 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b69 / 297 = 0.232$$c2021$$dQ1$$eT1
000130077 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b50 / 179 = 0.279$$c2021$$dQ2$$eT1
000130077 592__ $$a1.176$$b2021
000130077 593__ $$aComputer Science Applications$$c2021$$dQ1
000130077 593__ $$aInorganic Chemistry$$c2021$$dQ1
000130077 593__ $$aSpectroscopy$$c2021$$dQ1
000130077 593__ $$aOrganic Chemistry$$c2021$$dQ1
000130077 593__ $$aPhysical and Theoretical Chemistry$$c2021$$dQ1
000130077 593__ $$aMolecular Biology$$c2021$$dQ1
000130077 594__ $$a6.9$$b2021
000130077 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000130077 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos J.J.
000130077 700__ $$0(orcid)0000-0002-8839-6796$$aMahía A.
000130077 700__ $$0(orcid)0000-0003-4058-2888$$aMaity R.$$uUniversidad de Zaragoza
000130077 700__ $$0(orcid)0000-0003-4358-9110$$aConde-Giménez M.
000130077 700__ $$0(orcid)0000-0002-6649-9153$$aAnoz-Carbonell E.$$uUniversidad de Zaragoza
000130077 700__ $$aBerlamont H.
000130077 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy A.$$uUniversidad de Zaragoza
000130077 700__ $$aTouati E.
000130077 700__ $$aMamat U.
000130077 700__ $$aSchaible U.E.
000130077 700__ $$0(orcid)0000-0002-4972-7476$$aGálvez J.A.$$uUniversidad de Zaragoza
000130077 700__ $$0(orcid)0000-0001-9033-8459$$aDíaz-de-Villegas M.D.
000130077 700__ $$aHaesebrouck F.
000130077 700__ $$0(orcid)0000-0003-2076-844X$$aAínsa J.A.$$uUniversidad de Zaragoza
000130077 700__ $$0(orcid)0000-0002-2879-9200$$aSancho J.$$uUniversidad de Zaragoza
000130077 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000130077 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000130077 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000130077 773__ $$g22, 18 (2021), 221810137 [25 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000130077 8564_ $$s3757476$$uhttps://zaguan.unizar.es/record/130077/files/texto_completo.pdf$$yVersión publicada
000130077 8564_ $$s3058458$$uhttps://zaguan.unizar.es/record/130077/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000130077 951__ $$a2024-01-22-15:25:39
000130077 980__ $$aARTICLE