Helicobacter pylori (H. pylori) is a group-1 definite pathogenic carcinogen that infects approximately half of the global population, yet no species-specific chemotherapy has yet been developed. It is previously discovered that H. pylori encodes an atypical dehydrogenase/isomerase FabX in the Type-II fatty acid biosynthesis pathway to produce unsaturated fatty acids (UFA) as well as superoxide (ROS). Here, it is demonstrated that FabX is essential for H. pylori growth and gastric colonization by retaining UFA synthesis and producing ROS, respectively, and is a species-specific anti-H. pylori drug target. The first small molecule inhibitor FBX-1991 against FabX, which inhibits the enzymatic activity with an IC