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Biomolecules 2018, 8(4), 122; https://doi.org/10.3390/biom8040122

Synergistic Effect of Combinations Containing EDTA and the Antimicrobial Peptide AA230, an Arenicin-3 Derivative, on Gram-Negative Bacteria

1
Université de Lorraine, CITHEFOR, F-54000 Nancy, France
2
MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, F-49933 Angers, France
3
Adenium Biotech ApS, DK-2200 Copenhagen, Denmark
4
Laboratoire de bactériologie, 49100 CHU Angers, France
5
Equipe ATIP AVENIR, CRCINA, Inserm, Université de Nantes, Université d’Angers, 49100 Angers, France
*
Author to whom correspondence should be addressed.
Received: 5 October 2018 / Revised: 18 October 2018 / Accepted: 19 October 2018 / Published: 23 October 2018
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Abstract

The worldwide occurrence of resistance to standard antibiotics and lack of new antibacterial drugs demand new strategies to treat complicated infections. Hence, the aim of this study was to examine the antibacterial activities of an antimicrobial peptide, arenicin-3 derivative AA230, and ethylenediaminetetraacetic acid (EDTA) as well as the two compounds in combination against Gram-negative bacteria. AA230 showed strong antibacterial activity against all of the studied standard strains and clinical isolates, with minimum inhibitory concentrations ranging between 1 µg/mL and 8 µg/mL. AA230 exhibited a bactericidal mode of action. EDTA inhibited the growth of Acinetobacter baumannii at 500–1000 µg/mL. Strains of Acinetobacter baumannii were found to be more susceptible to EDTA than Pseudomonas aeruginosa or Escherichia coli. The antibacterial effects of both AA230 and EDTA were independent of the antibiotic resistance patterns. Indifference to synergistic activity was observed for AA230 and EDTA combinations using checkerboard titration. In time-kill studies, a substantial synergistic interaction between AA230 and EDTA was detected against all of the tested strains. The addition of EDTA enabled a 2–4-fold decrease in the AA230 dose. In conclusion, AA230 could have potential applications in the treatment of infections caused by Gram-negative organisms, and its effect can be potentiated by EDTA. View Full-Text
Keywords: antimicrobial peptides; synergy; arenicin; EDTA; gram-negative bacteria; antibiotic resistance; Acinetobacter baumannii; Escherichia coli; Pseudomonas aeruginosa; ESKAPE pathogens antimicrobial peptides; synergy; arenicin; EDTA; gram-negative bacteria; antibiotic resistance; Acinetobacter baumannii; Escherichia coli; Pseudomonas aeruginosa; ESKAPE pathogens
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Umerska, A.; Strandh, M.; Cassisa, V.; Matougui, N.; Eveillard, M.; Saulnier, P. Synergistic Effect of Combinations Containing EDTA and the Antimicrobial Peptide AA230, an Arenicin-3 Derivative, on Gram-Negative Bacteria. Biomolecules 2018, 8, 122.

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