Gram-negative antibiotic that preserves commensal bacteria

A Gram-negative-selective antibiotic could help treat infections while preserving the microbiome by targeting the Gram-negative-specific Lol lipoprotein transport system, which has low homology between Gram-negative commensal bacteria and pathogens.

Previous screens identified two compounds, a pyridinepyrazole and a pyridineimidazole, as inhibitors of the essential LolCDE transporter complex in Gram-negative bacteria, that were not developed as drugs due to poor in vivo efficacy, solubility, and other metrics. ...