000088402 001__ 88402
000088402 005__ 20230622083309.0
000088402 0247_ $$2doi$$a10.3390/microorganisms8040503
000088402 0248_ $$2sideral$$a117116
000088402 037__ $$aART-2020-117116
000088402 041__ $$aeng
000088402 100__ $$0(orcid)0000-0002-0531-0943$$aGonzález Rodríguez, Andrés$$uUniversidad de Zaragoza
000088402 245__ $$aSmall molecule inhibitors of the response regulator ArsR exhibit bactericidal activity against Helicobacter pylori
000088402 260__ $$c2020
000088402 5060_ $$aAccess copy available to the general public$$fUnrestricted
000088402 5203_ $$aHelicobacter pylori is considered the most prevalent bacterial pathogen in humans. The increasing antibiotic resistance evolved by this microorganism has raised alarm bells worldwide due to the significant reduction in the eradication rates of traditional standard therapies. A major challenge in this antibiotic resistance crisis is the identification of novel microbial targets whose inhibitors can overcome the currently circulating resistome. In the present study, we have validated the use of the essential response regulator ArsR as a novel and promising therapeutic target against H. pylori infections. A high-throughput screening of a repurposing chemical library using a fluorescence-based thermal shift assay identified several ArsR binders. At least four of these low-molecular weight compounds noticeably inhibited the DNA binding activity of ArsR and showed bactericidal effects against antibiotic-resistant strains of H. pylori. Among the ArsR inhibitors, a human secondary bile acid, lithocholic acid, quickly destroyed H. pylori cells and exhibited partial synergistic action in combination with clarithromycin or levofloxacin, while the antimicrobial effect of this compound against representative members of the normal human microbiota such as Escherichia coli and Staphylococcus epidermidis appeared irrelevant. Our results enhance the battery of novel therapeutic tools against refractory infections caused by multidrug-resistant H. pylori strains.
000088402 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$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
000088402 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000088402 590__ $$a4.128$$b2020
000088402 591__ $$aMICROBIOLOGY$$b52 / 136 = 0.382$$c2020$$dQ2$$eT2
000088402 592__ $$a0.857$$b2020
000088402 593__ $$aMicrobiology$$c2020$$dQ2
000088402 593__ $$aVirology$$c2020$$dQ2
000088402 593__ $$aMicrobiology (medical)$$c2020$$dQ2
000088402 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000088402 700__ $$aCasado, Javier
000088402 700__ $$aChueca, Eduardo
000088402 700__ $$0(orcid)0000-0003-0195-5434$$aSalillas, Sandra$$uUniversidad de Zaragoza
000088402 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000088402 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000088402 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000088402 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000088402 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000088402 773__ $$g8, 4 (2020), 503 [16 pp.]$$pMicroorganisms$$tMicroorganisms$$x2076-2607
000088402 8564_ $$s2714172$$uhttps://zaguan.unizar.es/record/88402/files/texto_completo.pdf$$yVersión publicada
000088402 8564_ $$s466118$$uhttps://zaguan.unizar.es/record/88402/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000088402 909CO $$ooai:zaguan.unizar.es:88402$$particulos$$pdriver
000088402 951__ $$a2023-06-21-14:59:21
000088402 980__ $$aARTICLE