Natural products that target the cell envelope.

The inexorable spread of resistance to clinically used drugs demands that we maintain a full pipeline of antibiotic candidates. As organisms have struggled to survive and compete over evolutionary history, they have developed the capacity to make a remarkably diverse array of natural products that target the cell envelope. A few have been developed for use in the clinic but most have not, and there are still an enormous number of opportunities to investigate. Substrate-binding antibiotics for Gram-positive organisms, phage-derived lysins, and outer membrane protein-targeting agents for Gram-negative organisms represent promising avenues where nature’s gifts may be repurposed for use in the clinic.