Antimicrobial and Antibiofilm Activities of New Synthesized Silver Ultra-NanoClusters (SUNCs) AgainstHelicobacter pylori

Helicobacter pyloricolonizes approximately 50% of the world's population, and it is the cause of chronic gastritis, peptic ulcer disease, and gastric cancer. The increase of antibiotic resistance is one of the biggest challenges of our century due to its constant increase. In order to identify an alternative or adjuvant strategy to the standard antibiotic therapy, thein vitroactivity of newly synthesized Silver Ultra-NanoClusters (SUNCs), characterized by an average size inferior to 5 nm, against clinical strains ofH. pylori, with different antibiotic susceptibilities, was evaluated in this study. MICs and MBCs were determined by the broth microdilution method, whereas the effect of drug combinations was determined by the checkerboard assay. The Minimum Biofilm Eradication Concentration (MBEC) was measured using AlamarBlue (AB) assay and colony-forming unit (CFU) counts. The cytotoxicity was evaluated by performing the MTT assay on the AGS cell line. The inhibitory activity was expressed in terms of bacteriostatic and bactericidal potential, with MIC50, MIC90, and MBC(50)of 0.33 mg/L against planktonicH. pyloristrains. Using the fractional inhibitory concentration index (FICI), SUNCs showed potential synergism with metronidazole and clarithromycin. The biofilm eradication was obtained after treatment with 2x, 3x, and 4x MIC values. Moreover, SUNCs showed low toxicity on human cells and were effective in eradicating a mature biofilm produced byH. pylori. The data presented in this study demonstrate that SUNCs could represent a novel strategy for the treatment ofH. pyloriinfections either alone or in combination with metronidazole.