Fig. 1. Approaches for discovery of antibiotics with novel mechanisms of action and improving activity of existing drugs. (A) The odilorhabdin (NOSO-95C) and darobactin were both isolated from nematode symbionts. Search for biosynthetic gene clusters similar to that of darobactin led to another inhibitor, dynobactin A. (B) Non-traditional culturing methods (e.g. iChip) have also enabled the culturing of bacterial species with currently untapped natural product repositories. (C) Implementation of physicochemical guidelines (eNTRY rules) has expanded the spectrum of originally Gram-positive-only antibiotics. Created with https://BioRender.com.