Antimicrobial resistance is a looming threat to global human health, and there is a burgeoning need for new and innovative ways to treat the illnesses caused by drug-resistant pathogens. Of particular concern is the rise in infections caused by gram-negative bacteria, as these are notoriously difficult to treat given the penetrability barrier of the gram-negative cellular envelope. The Hergenrother lab has developed a set of predictive guidelines, known as the “eNTRy Rules,” that help ascertain whether a small molecule drug will penetrate and accumulate in E. coli, a gram-negative pathogen. This has been incredibly useful for the target conversion of gram-positive-only drugs to broad-spectrum agents, yet there is still untapped potential for drugs that inherently exceed some of the eNTRy parameters. My research focuses on developing a prodrug strategy for these types of compounds that have high translational potential.