000079787 001__ 79787
000079787 005__ 20200716101508.0
000079787 0247_ $$2doi$$a10.1038/s41598-019-47746-9
000079787 0248_ $$2sideral$$a112618
000079787 037__ $$aART-2019-112618
000079787 041__ $$aeng
000079787 100__ $$0(orcid)0000-0002-0531-0943$$aGonzález, Andrés$$uUniversidad de Zaragoza
000079787 245__ $$aIdentifying potential novel drugs against Helicobacter pylori by targeting the essential response regulator HsrA
000079787 260__ $$c2019
000079787 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079787 5203_ $$aThe increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome the current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. pylori infection. We screened 1120 FDA-approved drugs for molecules that bind to the essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as HsrA binders. All of these compounds noticeably inhibited the in vitro DNA binding activity of HsrA, but only four of them, apigenin, chrysin, kaempferol and hesperetin, exhibited high bactericidal activities against H. pylori. Chrysin showed the most potent bactericidal activity and the most synergistic effect in combination with clarithromycin or metronidazole. Flavonoid binding to HsrA occurs preferably at its C-terminal effector domain, interacting with amino acid residues specifically involved in forming the helix-turn-helix DNA binding motif. Our results validate the use of HsrA as a novel and effective therapeutic target in H. pylori infection and provide molecular evidence of a novel antibacterial mechanism of some natural flavonoids against H. pylori. The results further support the valuable potential of natural flavonoids as candidate drugs for novel antibacterial strategies.
000079787 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MINECO/FJCI-2014-20704$$9info:eu-repo/grantAgreement/ES/MINECO/IJCI-2016-27419
000079787 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000079787 590__ $$a3.998$$b2019
000079787 591__ $$aMULTIDISCIPLINARY SCIENCES$$b17 / 71 = 0.239$$c2019$$dQ1$$eT1
000079787 592__ $$a1.341$$b2019
000079787 593__ $$aMultidisciplinary$$c2019$$dQ1
000079787 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000079787 700__ $$0(orcid)0000-0003-0195-5434$$aSalillas, Sandra$$uUniversidad de Zaragoza
000079787 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000079787 700__ $$0(orcid)0000-0002-3268-8730$$aEspinosa Angarica, Vladimir
000079787 700__ $$0(orcid)0000-0001-8644-4574$$aFillat, María F.$$uUniversidad de Zaragoza
000079787 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000079787 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000079787 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000079787 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000079787 773__ $$g9, 11294 (2019)$$pSci. rep.$$tScientific Reports$$x2045-2322
000079787 8564_ $$s2311817$$uhttps://zaguan.unizar.es/record/79787/files/texto_completo.pdf$$yVersión publicada
000079787 8564_ $$s109764$$uhttps://zaguan.unizar.es/record/79787/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000079787 909CO $$ooai:zaguan.unizar.es:79787$$particulos$$pdriver
000079787 951__ $$a2020-07-16-09:17:06
000079787 980__ $$aARTICLE