Short antibacterial peptides and erythromycin act synergically against Escherichia coli

Abstract

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 exerted differences in their mode of action. To gain a better understanding of the possible mode of action of these peptides, they were studied in combination with clinically used antibiotics with different targets. Antibiotic-peptide combinations were tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. No synergy was observed between the peptides and antibiotics when tested against S. aureus. Synergic interactions between 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 synergically or antagonistically and the number of residues. We further investigated the combined action of our peptides and PGLa, to elucidate peptide-peptide interactions. In contrast to previously reported synergy between magainin 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 antibacterial peptides as compared with peptides such as magainin 2.

In VitroandIn VivoSynergistic Effects of Cryptdin 2 and Ampicillin against Salmonella

“…These results are in concordance with earlier reports suggesting a synergetic effect of antimicrobial peptides with ␤-lactam antibiotics (16,36). The most interesting finding of our study was that the addition of cryptdin 2 not only potentiated the effectiveness of ampicillin but also reduced the therapeutic dosage of both agents to half (from 5 g to 2.5 g per mouse of cryptdin 2 and from 16, 32, and 64 mg/kg to 8, 16, and 32 mg/kg of Amp) while maintaining the increased therapeutic efficacy, compared with that of the drugs alone, against experimental salmonellosis.…”

“…This can be attributed to an increased permeability of the Salmonella cell membrane created by cryptdin 2, thereby leading to an increased diffusion of Amp into the intracellular targets. These observations are consistent with previous studies pertaining to the synergetic actions of ␣-helical peptide p18, reproductive tract beta-defensins, HNP-1, magainin, cathelicidins, and several other novel cationic peptides with commonly used antibiotics against Escherichia coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloacae (7,16,32,36,37).…”

Efficacy of Cryptdin-2 as an Adjunct to Antibiotics from Various Generations Against Salmonella

“…These two mechanisms might have acted mutually leading to make this very combination to be the most effective amongst all the combinations tested. These observations are consistent with previous studies pertaining to the synergetic actions of a-helical peptide p18, reproductive tract beta-defensins, HNP-1, magainin, cathelicidins and several other novel cationic peptides with commonly used antibiotics against Escherichia coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae [26,27].…”

Porphyromonas gingivalis Cysteine Proteinase Inhibition by κ-Casein Peptides

“…FIC calculations have been recently applied to short antimicrobial peptides such as magainin and gaegurin against Gram-negative and Gram-positive bacteria and, according to this index, -casein(109-137) exhibited synergism with ZnCl 2 (16,24,25,46).…”