Short antibacterial peptides and erythromycin act synergically against Escherichia coli

Five different peptides (6-18 residues) with chain lengths shorter than the required minimum to span the bacterial cell membrane as monomeric helices were designed in order to elucidate whether variation in chain length exert ed differences in their mode of action. To gain a better understanding of t he possible mode of action of these peptides, they were studied in combinat ion with clinically used antibiotics with different targets. Anti biotic-pe ptide combinations were tested against Escherichia coil ATCC 25922 and Stap hylococcus aureus ATCC 25923. No synergy was observed between the peptides and antibiotics when tested against S. aureus. Synergic interactions betwee n all peptides and erythromycin were observed when tested against E. coli. Synergy was also observed with rifampicin and two peptides against E. coli. There was no clear-cut correlation between the ability to interact synergi cally or antagonistically and the number of residues. We further investigat ed the combined action of our peptides and PGLa, to elucidate peptide-pepti de interactions. In contrast to previously reported synergy between magaini n 2 and PGLa, our peptides did not show any synergy when combined with PGLa . Thus, our results indicate an alternative mode of action of these antibac terial peptides as compared with peptides such as magainin 2.