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Here, we report an effective way of enhancing and restoring the antibacterial activity of inactive antibiotics by applying them together with a\u00a0cyanographene\/Ag nanohybrid, a nanomaterial that is applied for the first time for restoring the antibacterial activity of antibiotics. The cyanographene\/Ag nanohybrid was synthesized by chemical reduction of a precursor material in which silver cations are coordinated on a cyanographene sheet. The\u00a0antibacterial efficiency of the combined treatment was evaluated by determining fractional inhibitory concentrations (FIC) for antibiotics with different modes of action (gentamicin, ceftazidime, ciprofloxacin, and colistin) against the strains <jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Pseudomonas aeruginosa,<\/jats:italic> and <jats:italic>Enterobacter kobei<\/jats:italic> with different resistance mechanisms. Synergistic and partial synergistic effects against multiresistant strains were demonstrated for all of these antibiotics except ciprofloxacin, which exhibited an additive effect. The lowest average FICs equal to 0.29 and 0.39 were obtained for colistin against <jats:italic>E. kobei<\/jats:italic> and for gentamicin against <jats:italic>E. coli<\/jats:italic>, respectively. More importantly, we have experimentally confirmed for the first time, that interaction between the antibiotic's mode of action and the mechanism of bacterial resistance strongly influenced the combined treatment\u2019s efficacy.<\/jats:p>","DOI":"10.1038\/s41598-022-09294-7","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T20:38:03Z","timestamp":1648240683000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Restoration of antibacterial activity of inactive antibiotics via combined treatment with a cyanographene\/Ag nanohybrid"],"prefix":"10.1038","volume":"12","author":[{"given":"Lucie","family":"Hochvaldov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pan\u00e1\u010dek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"V\u00e1lkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Prucek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u011bra","family":"Kohlov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Ve\u010de\u0159ov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Kol\u00e1\u0159","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libor","family":"Kv\u00edtek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ale\u0161","family":"Pan\u00e1\u010dek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"9294_CR1","first-page":"1","volume":"1","author":"CJ Graham","year":"2017","unstructured":"Graham, C. 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