A green synthesis route was developed for preparation of the ZnO nanoparticles and ZnO/CuO nanocomposites by using Vaccinium arctostaphylos L. fruit extract, and their anti-bacterial activities against two pathogenic bacteria, Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive), were investigated. The fabricated nanomaterials were characterized by XRD, EDX, FESEM, TEM, TGA, FT-IR, UV–vis DRS and BET instruments. The results showed that the sizes of ZnO and CuO nanoparticles in the ZnO/CuO (10%) nanocomposite were 12 and 8 nm, respectively. In addition, specific surface areas of the ZnO (W), ZnO (ext) and ZnO/CuO samples were 29.3, 27.5 and 18.0 m²/g⁻¹, respectively. The results obtained from EDX, TGA, FT-IR and UV–Vis DRS analyses displayed that some of the organic compounds from the fruit extract have bonded to the surface of the samples fabricated in the presence of the fruit extract. The results revealed that the anti-bacterial activity of the fabricated samples is as ZnO/CuO (10%) > ZnO/CuO (5%) > ZnO (ext) > ZnO (W). Viability percentages for E. coli and S. aureus bacteria were 12.1 ± 0.39 and 14.9 ± 0.65 in the presence of the ZnO/CuO (10%) nanocomposite, respectively. The SEM images clearly demonstrated the disruption of the bacterial membranes during the inactivation process. Graphical Abstract

During the last decades, increase of antibiotic resistance among pathogenic bacteria has been considered as a global concern. Therefore, it is important to find new antimicrobial agents and/or therapeutic strategies. In previous studies we investigated antibacterial activity of the CM11 peptide against multiple drug resistant clinical isolates of six bacteria species including Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Salmonella typhimurium. In this study, in order to reduce treatment costs and the cytotoxic effect of CM11 peptide, was analyzed its synergic interaction with selected antibiotics. In this reason, specific antibiotics for each bacterium were selected considering the guidelines of the "Clinical and Laboratory Standards Institute". Based on the results , using a checkerboard procedure through the broth microdilution method, MICs of antibiotic agents alone and in combination with the peptide were determined. In most cases, synergistic effects between CM11 peptide and selected antibiotics against six bacteria species were observed as partial synergy. However, for S. aureus and P. aeruginosaa synergic interaction between peptide and selective antibiotics was observed with penicillin and ceftazidime, respectively. For K. pneumoniae, synergic effect was observed when CM11 peptide was used in combination with norfloxacin and also the combination of peptide with norfloxacin showed synergic effect against A. baumannii. Combination between the CM11 peptide and ciprofloxacin showed synergic effect on E. coli while only partial synergy was observed for S. typhimurium in combination with cefotaxime and ceftazidime. These results suggest that when selected antibiotic used in combination with the CM11 peptide, the dose of some antibiotics, especially the dose independent antibiotics, may be reduced for eliminating drug resistant bacteria.