Unacylated tridecaptin A₁ acts as an effective sensitiser of Gram-negative bacteria to other antibiotics.

A derivative of the linear cationic lipopeptide tridecaptin A₁missing the N-terminal lipophilic acyl group, termed H-TriA₁, is devoid of antimicrobial activity but is extremely effective at sensitising Gram-negative bacteria to certain antibiotics. H-TriA₁has low cytotoxicity compared with the natural peptide and in low concentrations it can substantially lower the minimum inhibitory concentration (MIC) of some antibiotics against strains of Escherichia coli, Campylobacter jejuni and Klebsiella pneumoniae. In particular, the MIC of rifampicin was lowered 256-512-fold against K. pneumoniae strains using low concentrations of H-TriA₁. H-TriA₁does not exert its synergistic effect through partial membrane lysis, but does bind to model bacterial membranes in a manner akin to the natural peptide. Formation of this stable secondary structure on the outer membrane may account for the observed synergistic activity.