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

Abstract

Helicobacter pylori colonizes 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, the in vitro activity of newly synthesized Silver Ultra-NanoClusters (SUNCs), characterized by an average size inferior to 5 nm, against clinical strains of H. 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 MIC 50 , MIC 90 , and MBC 50 of 0.33 mg/L against planktonic H. pylori strains. Using the fractional inhibitory concentration index (FICI), SUNCs showed potential synergism with metronidazole and clarithromycin. The biofilm eradication was obtained after treatment with 2×, 3×, and 4× MIC values. Moreover, SUNCs showed low toxicity on human cells and were effective in eradicating a mature biofilm produced by H. pylori. The data presented in this study demonstrate that SUNCs could represent a novel strategy for the treatment of H. pylori infections either alone or in combination with metronidazole.

Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship

“…The treatment of H. pylori infection now also includes the new synthesized silver ultra-nanoclusters (SUNCs) alone or in combination with metronidazole ( Grande et al, 2020 ). The development of biofilms by bacterial populations represents the main virulence factor in many localized chronic infections ( Koo et al, 2017 ).…”

“…The development of biofilms by bacterial populations represents the main virulence factor in many localized chronic infections ( Koo et al, 2017 ). The hypothesis behind the SUNC effectiveness for eradication of H. pylori infection relies on the ability of the nanoparticles to penetrate through the biofilm extracellular polymeric substances matrix: SUNCs can then disrupt the biofilm to induce cell death, and also promote cell detachment from the surface, and reduce drug resistance ( Grande et al, 2020 ). These SUNCs also provide the possibility of carriers for drug delivery ( Grande et al, 2020 ).…”

Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

“…Among the first cluster of alkyloxy derivatives (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), the MIC results demonstrated no or weak efficacy against all the strains as well as their parent compound, despite the presence of branched alkyl chains, unsaturations or specific functional groups (ketone, carboxylic acid, ethyl ester). Only three derivatives (3,9,12) with linear and increasing alkyl chains (Et, n-Pr, n-Bu) presented improved MIC values with respect to thymol against some clinical isolates (MIC/MBC = 16 µg/mL).…”

“…About 50% of the global population is colonized by the microorganism although in most cases H. pylori causes no symptoms [4]. The survival of the microorganism as well as the recalcitrance of the infection are due to H. pylori aptitude to adapt itself to the host and to develop resistance towards the antimicrobials commonly used in therapy [5]. The resistance rate to the clinically approved drugs is increasing worldwide and most of the therapeutic failures are ascribed to adaptive mechanisms linked to the biofilm formation [6], which limit the efficacy of the current therapy.…”

Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of H. pylori Strains and AGS Cell Proliferation

“…H. pylori , a microaerophilic Gram-negative bacterium, colonizes about the 50% of the world’s population representing the causative agent of the development of chronic gastritis, peptic ulcer and gastric cancer [ 7 ]; for the latter, it has been recognized as a class I carcinogen by the World Health Organization. Gastric cancer represents the third most common cancer worldwide [ 7 , 8 ] and epidemiological studies demonstrated that the eradication of H. pylori induces a decrease of incidence of such malignancy [ 9 ]. The triple therapy, consisting of a proton-pump inhibitor (PPI) and two different antimicrobial drugs, represented the anti- H. pylori standard therapy for the last 20 years.…”