In vitro activity of a new artemisinin derivative against Helicobacter pylori and its effect on biofilm formation

Abstract

Artemisinin and its derivatives are widely used as antimalarial drugs, and are also active against extracellular and intracellular Helicobacter pylori. Here we investigated the in vitro activity of the new artemisinin derivative GC012 against the reference strain H. pylori ATCC 43504 and 25 clinical isolates with different antibiotic susceptibility patterns by using the microdilution method. The bactericidal activity was also evaluated by time-kill curves on the reference strain ATCC 43504. The growth inhibitory concentrations of GC012 against the clinical isolates were the same as bactericidal action, with values ranging from 0.125 to 0.03 μg/mL. A decrease of 6-log10 in cell count was observed after 48 hours at the MIC value of 0.06 μg/mL. The antibiotic treatment alters the gastrointestinal microflora and induces a dysbiosis. For this reason, GC012 was tested against nine bacterial strains including five Gram negative and four Gram positive bacteria and two yeast strains to mimic genera harboured in the intestinal microbiota; GC012 was inactive against both the bacteria and the yeasts. H. pylori forms biofilms in the human host and in the environment (ie, water sources). Thus, we evaluated the effect of GC012 on biofilm formation by a clinical strain. Preliminary results showed approximately 60% reduction of biofilm with respect to the untreated control, after treatment with 0.06 μg/mL of GC012 (½ MIC for this strain); no effect was observed at lower concentrations. Overall, the activities of artemisinins suggest that they can be considered as a valid alternative therapy for the treatment of H. pylori infection