Anti-microbial compositions for inhibiting gram-negative bacterial growth include inhibitors of one or more interactions between the bacterial proteins TonB and ExbD and/or between the bacterial proteins TolR and TolA. Methods of producing and using the anti-microbial compositions (e.g., treating gram-negative bacterial infections in a mammalian subject) are described. Novel antibiotics that target the TonB system and prevent bacterial growth are described herein.