Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class

In an era of escalating antibiotic resistance, there is a pressing need for innovative strategies to develop novel antibiotics. Gram-negative bacteria, characterized by their robust dual-membrane, are intrinsically resistant to a wide range of antibiotics and can readily develop new resistances. Members of this bacterial class comprise numerous pathogenic organisms, including the primary cause of gastric cancer, Helicobacter pylori. In this study, we used the Giga-sized collection of theoretical molecules inside Enamine's REAL Space to identify inhibitors for H. pylori glutamate racemase. These compounds displayed a diverse range of activity in preventing H. pylori growth, with our most potent hits capable of selective full growth inhibition for metronidazole and clarithromycin resistant H. pylori strains. Alongside the introduction of a novel antibiotic class for this carcinogenic pathogen, our unique implementation of REAL Space holds great promise for Gram-negative antibiotic development as a whole.