New Weapons For Fighting Bacterium Behind Ulcers

The ulcer-causing bacterium Helicobacter pylori colonizes the guts of roughly half the world’s population, and there’s no easy way to treat infections. Standard antibiotics, such as amoxicillin and clarithromycin, tend to wipe out much of the gut’s healthy bacteria while battling H. pylori. What’s more, H. pylori has developed resistance to such treatments. To selectively target H. pylori over other bacteria, researchers led by Peter C. Tyler and Keith Clinch of Victoria University of Wellington and Vern L. Schramm of Albert Einstein College of Medicine set their sights on a novel enzymatic pathway in the bacterium (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b06110). H. pylori uses the enzyme 5ʹ-methylthioadenosine/S-adenosylhomocysteine nucleosidase, or MTAN, in its biosynthesis of menaquinone—a compound that’s essential for electron transport in the bacterium. Although other bacteria have MTANs, they’re not necessary for survival. By locking onto the transition state of H. pylori’s MTAN, the researchers reasoned they could selectively kill the bacterium. They developed 10 MTAN inhibitors (example shown) that do just that, halting H. pylori’s growth at low concentrations.