Searching for New Tools to Counteract the Helicobacter pylori Resistance: The Positive Action of Resveratrol Derivatives.

Paola Di Fermo,Rosa Amoroso,Silvia Di Lodovico,Barbara De Filippis,Emanuela Di Campli,Simonetta D’Ercole,Luigina Cellini,Mara Di Giulio

doi:10.3390/antibiotics9120891

Paola Di Fermo, Rosa Amoroso + Show 6 more

Open Access

https://doi.org/10.3390/antibiotics9120891

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Journal: Antibiotics	Publication Date: Dec 10, 2020
Citations: 20	License type: CC BY 4.0

Affiliation: University of Chieti-Pescara

Abstract

The drug-resistance phenomenon in Helicobacter pylori underlines the need of novel strategies to improve the eradication rate including alternative treatments combining antibiotic and non-antibiotic compounds with synergistic action. In this study, the antibacterial (MIC/MBC) and anti-virulence effects (biofilm reduction and swarming motility inhibition) of resveratrol-RSV and new synthetized RSV-phenol derivatives, with a higher bioavailability, alone and combined with levofloxacin-LVX were evaluated against resistant H. pylori clinical strains. The experiments were confirmed in vivo using the Galleria mellonella model. Among the studied RSV derivatives, RSV-3 and RSV-4 possessed higher antibacterial activity with respect to RSV (MICs from 6.25 to 200 µg/mL and from 3.12 to 200 µg/mL, respectively). RSV, RSV-3, and RSV-4 were able to synergize with LVX restoring its effect in two out of seven clinical resistant strains tested for the study. RSV, RSV-3, and RSV-4, alone and with LVX at sub-MIC and sub-synergistic concentrations, significantly reduced the biofilm formation. Moreover, RSV-3 and RSV-4 reduced the H. pylori swarming motility on soft agar. RSV, RSV-3, and RSV-4 were non-toxic for G. mellonella larvae and displayed a protective effect against H. pylori infection. Overall, RSV–phenol derivatives should be considered interesting candidates for innovative therapeutic schemes to tackle the H. pylori antibiotic resistance.

Highlights

Helicobacter pylori is a gastroduodenal pathogen that affects more than 60% of the population worldwide with a higher prevalence in developing countries [1]
In the first step of this study, we evaluated the antibacterial effect of RSV and new synthetized derivatives, RSV-1–5, against resistant H. pylori clinical strains
The antibacterial activity of RSV has been described, based on more than a single mechanism, such as alteration of the lipid bilayer of the membrane and its permeability, changes in intracellular functions induced by hydrogen bonding of the phenolic group in 4-position to enzymes, and antioxidant-scavenging activity that could inhibit the generation of reactive oxygen species, reducing the redox potential of the growth medium [41,42,43,44]

Summary

Introduction

Helicobacter pylori is a gastroduodenal pathogen that affects more than 60% of the population worldwide with a higher prevalence in developing countries [1]. This bacterium is able to colonize the human stomach, thereby inducing inflammation of the gastric mucosa causing chronic or atrophic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer [2,3]. In our region (Abruzzo region), the resistance of H. pylori isolates to clarithromycin is high with values near 73% [4,5].

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