Expanded Gram-Negative Activity of Marinopyrrole A

The rise of bacterial infections is a global health issue that calls for the development and availability of additional antimicrobial agents. Known for its in vitro effects on Gram-positive organisms, the drug-like small molecule marinopyrrole A was re-examined for the potential of broader efficacy against a wider array of microbes. We uncovered selective efficacy against an important subset of Gram-negative bacteria from three genera: <i>Neisseria</i>, <i>Moraxella</i>, and <i>Campylobacter</i>. This susceptibility is correlated with the absence of canonical LPS in these specific Gram-negative species, a phenomenon observed with other hydrophobic anti-microbial compounds. Further, when exposed to molecules which inhibit the LpxC enzyme of the LPS synthesis pathway, previously resistant LPS-producing Gram-negative bacteria showed increased susceptibility to marinopyrrole A. These results demonstrate marinopyrrole A's efficacy against a broader range of Gram-negative bacteria than previously known, including <i>N. gonorrhea</i>, a species identified as a priority pathogen by the WHO.