Princeton Chemists Attach a Cell-Penetrating Peptide to Lasso Peptide Antibiotics, Extending Them to All Four Gram-Negative ESKAPE Pathogens
Princeton University chemists reported in ACS Chemical Biology on October 27, 2026 that conjugating a cell-penetrating peptide to the loop of the lasso peptides citrocin and microcin J25, which kill bacteria by blocking RNA polymerase but depend on specific transporters to get inside, gave them activity against all four Gram-negative ESKAPE pathogens. The conjugates were more potent than the parent peptides, with minimum inhibitory concentrations from high nanomolar to single micromolar, and entered E. coli through both transporter-dependent and transporter-independent routes, which the authors say could limit one path to resistance. The work is in bacterial cultures.