NATURE | A new paper on the treatment of infections caused by Gram-negative pathogens offers a strategy for the rational design of diazabicyclooctane inhibitors of penicillin-binding proteins. This study, co-authored by colleagues at Entasis Therapeutics, discusses what led to the discovery of ETX0462, a promising candidate offering “potent in vitro and in vivo activity against Pseudomonas aeruginosa plus all other Gram-negative ESKAPE pathogens, Stenotrophomonas maltophilia and biothreat pathogens”. It is also a CARB-X-funded program.