Helicobacter pylori is a bacterium that is responsible for the majority of peptic ulcers and is a risk factor for stomach cancer. It is present in the gut of more than half the world’s population. The treatment of H. pylori infections is complicated by the growing threat of resistance to traditional antibiotics.
A more targeted approach to fighting H. pylori might circumvent such problems. This bacterium has an unusual mechanism for producing menaquinone, an essential vitamin, in which the enzyme 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) plays a vital role.
Vern Schramm, Albert Einstein College of Medicine, New York, USA, Peter Tyler, Victoria University of Washington, New Zealand, and colleagues hope that disruption of this pathway is lethal to H. pylori. They synthesized 16 new compounds that structurally mimic the natural substrate of MTAN. Of these, ten were found to prevent the growth of the bacterium at concentrations up to 2000 times smaller than conventional antibiotics.
Validation of MTAN as a drug target, and the success of this initial screen are promising starts for new treatments against this bacterium which affects the health of millions.
- New Antibiotic Candidates Against Helicobacter pylori,
Shanzhi Wang, Scott A. Cameron, Keith Clinch, Gary B. Evans, Zhimeng Wu, Vern L. Schramm, Peter C. Tyler,
J. Am. Chem. Soc. 2015.