131847 20260217205512.0 doi 10.1128/spectrum.02623-23 sideral 137192 ART-2024-137192 eng Beyria, Lilha Antimicrobial combinations against Helicobacter pylori including benzoxadiazol-based flavodoxin inhibitors: in vitro characterization 2024 Access copy available to the general public Unrestricted Antimicrobial resistance of Helicobacter pylori (Hp) threatens currently available treatment regimens and prompts the development of antimicrobial drugs against new bacterial targets. One such class of drugs is Hp-flavodoxin (Hp-fld) inhibitors, which target an essential metabolic pathway in Hp. The aim of this study was to characterize the effects of these inhibitors against Hp over time when used alone or combined with conventional antibiotics. Four benzoxadiazol-based fld inhibitors were initially tested for their in vitro potency, with compound IV displaying the highest efficacy. This compound was then combined with clarithromycin, metronidazole, amoxicillin, levofloxacin, and rifampicin in further experiments. Checkerboard assays indicated that compound IV exhibited additive activity when combined with these antibiotics. The study further investigated the time course of antibacterial effects by exposing a high inoculum of Hp to compound IV and each antibiotic, alone or in combination. At just four times the minimum inhibitory concentration, compound IV demonstrated bactericidal effects within 6 h. However, the regrowth of bacteria occurred between 24 and 48 h of exposure. Similar patterns of killing followed by regrowth were observed for conventional antibiotics alone. However, the addition of compound IV to the antibiotics clearly limited regrowth over 72 h. These findings suggest that compound IV can effectively eliminate spontaneous mutants that are resistant to conventional antibiotics or prevent new mutations during drug exposure. Hp-fld inhibitors, such as compound IV, hold promise as new drugs to be integrated into Hp infection treatment, potentially reducing the development of resistance and shortening the duration of treatment. info:eu-repo/grantAgreement/ES/DGA/E45-20R info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.8 2024 MICROBIOLOGY 58 / 163 = 0.356 2024 Q2 T2 1.149 2024 Immunology and Microbiology (miscellaneous) 2024 Q1 Microbiology (medical) 2024 Q1 Ecology 2024 Q1 Physiology 2024 Q1 Infectious Diseases 2024 Q1 Genetics 2024 Q2 Cell Biology 2024 Q2 5.8 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gourbeyre, Ophelie Salillas, Sandra Universidad de Zaragoza (orcid)0000-0003-0195-5434 Mahía, Alejandro (orcid)0000-0002-8839-6796 Díaz de Villegas, María Dolores (orcid)0000-0001-9033-8459 Aínsa, José Antonio Universidad de Zaragoza (orcid)0000-0003-2076-844X Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 Bousquet-Mélou, Alain Ferran, Aude A. 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 1 (2024), e02623-23 [12 pp.] Microbiol. spectr. Microbiology Spectrum 2165-0497 579881 http://zaguan.unizar.es/record/131847/files/texto_completo.pdf Versión publicada 2217613 http://zaguan.unizar.es/record/131847/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:131847 articulos driver 2026-02-17-20:25:38 ARTICLE