Abstract
In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (no. 81373445, Y. X. C.), the Innovative Team of Peptide Drugs of Jilin Province (no. 20121807, Y. X. C.), the Natural Science Foundation of Jilin Province (no. 20140101042JC, Y. B. H.) and a Basic Scientific Research Grant from Jilin University (Y. X. C. and Y. B. H.).
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Figure S1
Analytical RP-HPLC chromatograms of purified peptides. Column: reversed-phase Zorbax SB-300-C8 (150-mm × 4.6-mm inner diameter); experiments were carried out with a linear AB gradient (1 % B/min) at a flow rate of 1 ml/min. Eluent A was 0.1 % aqueous trifluoroacetic acid (TFA) and eluent B was 0.1 % TFA in acetonitrile. The sequences of the peptides are shown in Table 1. (GIF 38 kb)
Figure S2
Mass spectra of peptides. Mass spectrometry analyses were conducted using an AB SCIEX MALDI TOF/TOF 5800 Analyzer (AB SCIEX, USA). Mass spectra were acquired in the reflector mode in the m/z 1,000–4,000 mass range. The sequences of the peptides are shown in Table 1. (GIF 42 kb)
Table S1
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Feng, Q., Huang, Y., Chen, M. et al. Functional synergy of α-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo. Eur J Clin Microbiol Infect Dis 34, 197–204 (2015). https://doi.org/10.1007/s10096-014-2219-3
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DOI: https://doi.org/10.1007/s10096-014-2219-3