Increased susceptibility to resveratrol of Helicobacter pylori strains isolated from patients with gastric carcinoma.

The increasing therapeutic failures against Helicobacter pylori infection has determined the need to develop new drugs. The susceptibility to resveratrol (1) of twenty-six H. pylori strains representing nine CagA+ strains from patients with gastric carcinoma and eight CagA- and nine CagA+ strains from patients with chronic gastritis only was evaluated. Compound 1 was dissolved in DMSO and double diluted in Brucella broth with 10% BFS; ca. 10(6) organisms were added to each dilution. After incubation, subcultures were performed using Columbia-blood agar plates. The lowest concentration in broth at which all the organisms were killed was considered the minimum bactericidal concentration (MBC). Tests were performed in triplicate. The mean MBC of 1 for CagA positive GC strains was significantly lower than those for both CagA positive and CagA negative CG strains. An F1 ATPase of H. pylori showed a significant linear homology with a human ATPase considered a possible target of 1. It was hypothesized that strains infecting patients with gastric carcinoma have a reduced expression of F-type ATPases, which normally protect the bacteria from low pH levels by maintaining a proton gradient across membranes. Such behavior can be considered as an adaptive response to decreased gastric acidity. Since the targets of resveratrol (1) are also the bacterial ATPases, their putative reduced expression could increase the susceptibility to this compound, so that it saturates its targets more quickly and efficiently.