Structure-Activity Relationship for the Picolinamide Antibacterials that Selectively Target .

is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. is difficult to eradicate due to its ability to form spores, which are not susceptible to antibiotics. To address the urgent need for treating recurrent infection, antibiotics that selectively target over common gut microbiota are needed. We herein describe the class of picolinamide antibacterials which show potent and selective activity against . The structure-activity relationship of 108 analogues of isonicotinamide , a compound that is equally active against methicillin-resistant and , was investigated. Introduction of the picolinamide core as exemplified by analogue resulted in exquisite potency and selectivity against . The ability of the picolinamide class to selectively target and to prevent gut dysbiosis holds promise for the treatment of recurrent infection.