000131847 001__ 131847
000131847 005__ 20250923084417.0
000131847 0247_ $$2doi$$a10.1128/spectrum.02623-23
000131847 0248_ $$2sideral$$a137192
000131847 037__ $$aART-2024-137192
000131847 041__ $$aeng
000131847 100__ $$aBeyria, Lilha
000131847 245__ $$aAntimicrobial combinations against Helicobacter pylori including benzoxadiazol-based flavodoxin inhibitors: in vitro characterization
000131847 260__ $$c2024
000131847 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131847 5203_ $$aAntimicrobial 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.
000131847 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00
000131847 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000131847 590__ $$a3.8$$b2024
000131847 592__ $$a1.149$$b2024
000131847 591__ $$aMICROBIOLOGY$$b58 / 163 = 0.356$$c2024$$dQ2$$eT2
000131847 593__ $$aImmunology and Microbiology (miscellaneous)$$c2024$$dQ1
000131847 593__ $$aMicrobiology (medical)$$c2024$$dQ1
000131847 593__ $$aEcology$$c2024$$dQ1
000131847 593__ $$aPhysiology$$c2024$$dQ1
000131847 593__ $$aInfectious Diseases$$c2024$$dQ1
000131847 593__ $$aGenetics$$c2024$$dQ2
000131847 593__ $$aCell Biology$$c2024$$dQ2
000131847 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131847 700__ $$aGourbeyre, Ophelie
000131847 700__ $$0(orcid)0000-0003-0195-5434$$aSalillas, Sandra$$uUniversidad de Zaragoza
000131847 700__ $$0(orcid)0000-0002-8839-6796$$aMahía, Alejandro
000131847 700__ $$0(orcid)0000-0001-9033-8459$$aDíaz de Villegas, María Dolores
000131847 700__ $$0(orcid)0000-0003-2076-844X$$aAínsa, José Antonio$$uUniversidad de Zaragoza
000131847 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000131847 700__ $$aBousquet-Mélou, Alain
000131847 700__ $$aFerran, Aude A.
000131847 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000131847 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000131847 773__ $$g12, 1 (2024), e02623-23 [12 pp.]$$pMicrobiol. spectr.$$tMicrobiology Spectrum$$x2165-0497
000131847 8564_ $$s579881$$uhttps://zaguan.unizar.es/record/131847/files/texto_completo.pdf$$yVersión publicada
000131847 8564_ $$s2217613$$uhttps://zaguan.unizar.es/record/131847/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131847 909CO $$ooai:zaguan.unizar.es:131847$$particulos$$pdriver
000131847 951__ $$a2025-09-22-14:33:33
000131847 980__ $$aARTICLE