88402 20230622083309.0 doi 10.3390/microorganisms8040503 sideral 117116 ART-2020-117116 eng González Rodríguez, Andrés Universidad de Zaragoza (orcid)0000-0002-0531-0943 Small molecule inhibitors of the response regulator ArsR exhibit bactericidal activity against Helicobacter pylori 2020 Access copy available to the general public Unrestricted Helicobacter 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. info:eu-repo/grantAgreement/ES/DGA/B25-17R info:eu-repo/grantAgreement/ES/DGA/E45-17R info:eu-repo/grantAgreement/ES/FIS/PI11-02578 info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/grantAgreement/ES/MINECO/FJCI-2014-20704 info:eu-repo/grantAgreement/ES/MINECO/IJCI-2016-27419 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.128 2020 MICROBIOLOGY 52 / 136 = 0.382 2020 Q2 T2 0.857 2020 Microbiology 2020 Q2 Virology 2020 Q2 Microbiology (medical) 2020 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Casado, Javier Chueca, Eduardo Salillas, Sandra Universidad de Zaragoza (orcid)0000-0003-0195-5434 Velázquez-Campoy, Adrián Universidad de Zaragoza (orcid)0000-0001-5702-4538 Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 Lanas, Ángel Universidad de Zaragoza (orcid)0000-0001-5932-2889 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 8, 4 (2020), 503 [16 pp.] Microorganisms Microorganisms 2076-2607 2714172 http://zaguan.unizar.es/record/88402/files/texto_completo.pdf Versión publicada 466118 http://zaguan.unizar.es/record/88402/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:88402 articulos driver 2023-06-21-14:59:21 ARTICLE