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Combination effect of epsilon-poly-L-lysine and antibiotics against common bacterial pathogens

The Journal of Antibiotics volume 75, pages 354–359 (2022)Cite this article

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Abstract

Epsilon-poly-l-lysine (EPL) is an antimicrobial peptide with low mammalian toxicity; thus, it is commonly used as food preservative. Here, the capacity of EPL to improve the efficacy of the antibiotics ampicillin (AMP), gentamycin (GEN), tetracycline (TCN), and methicillin (MET) against four bacterial pathogens, namely Pseudomonas aeruginosa PAO1, Klebsiella pneumoniae CG43, MET-sensitive Staphylococcus aureus ATCC 25923 (MSSA), and MET-resistant S. aureus ATCC 33591 (MRSA), was investigated. Some antibiotic–EPL combinations, i.e., AMP–EPL, GEN–EPL, and TCN–EPL, were particularly active against the pathogens through synergy, partial synergy, or additive effects. Additionally, MET–EPL displayed a partial synergistic effect against MRSA. GEN–EPL had the most powerful antimicrobial effect against MSSA: it eradicated the bacterium within an hour. Conversely, AMP–EPL and MET–EPL were the least potent combinations against MRSA, and TCN–EPL was least potent against K. pneumoniae; for these combinations, bactericidal activities occurred >10 h after initial treatments. All antibiotic–EPL treatments showed inhibitory activities against P. aeruginosa biofilm formation and enhanced preformed biofilm disruption in vitro. Similarly, the inhibition of biofilm formation on a porcine skin model was observed. Moreover, no significant cytotoxicity was detected for any antibiotic–EPL treatment in tests using Balb/3t3 fibroblasts. Given the rise in antibiotic-resistant bacteria, combining antibiotics with EPL may enhance antibiotic effectiveness, as shown in this study, while helping to avoid antimicrobial resistance.

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Acknowledgements

This work is supported by the Ministry of Science and Technology (MOST) (Grant number: 109-2320-B-007-007-MY3), Taiwan.

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  1. Institute of Molecular Medicine, National Tsing Hua University, Hsin Chu, Taiwan, ROC

    Sneha Sundaran, Li-Ching Kok & Hwan-You Chang

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  1. Sneha Sundaran
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Correspondence to Hwan-You Chang.

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Sundaran, S., Kok, LC. & Chang, HY. Combination effect of epsilon-poly-L-lysine and antibiotics against common bacterial pathogens. J Antibiot 75, 354–359 (2022). https://doi.org/10.1038/s41429-022-00523-9

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