POLYMYXIN B OCTAPEPTIDE AND POLYMYXIN B HEPTAPEPTIDE ARE POTENT OUTER MEMBRANE PERMEABILITY-INCREASING AGENTS

Abstract

Polymyxin B octapeptide (PBOP) and polymyxin B heptapeptide (PBHP) were found to be effective permeabilizers of the outer membrane of Escherichia coli and Salmonella typhimurium. PBOP was as effective as polymyxin B nonapeptide (PMBN), the known very potent permeabilizer. As low a PBOP concentration as 1μg/ml sensitized E. coli to rifampicin by a factor of 100. Three μg of PBOP per ml was sufficient to sensitize this target to all the other tested hydrophobic antibiotics (erythromycin, fusidic acid, clindamycin, and novobiocin) by a factor of 30. Only a slightly higher (3-fold) concentration of PBHP was required for a similar sensitizing effect.