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. 2018 Oct 23;8(4):122.
doi: 10.3390/biom8040122.

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

Anita Umerska  1   2 , Magnus Strandh  3 , Viviane Cassisa  4 , Nada Matougui  5 , Matthieu Eveillard  6 , Patrick Saulnier  7
Affiliations

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

Anita Umerska et al. Biomolecules. .

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.

Keywords: Acinetobacter baumannii; EDTA; ESKAPE pathogens; Escherichia coli; Pseudomonas aeruginosa; antibiotic resistance; antimicrobial peptides; arenicin; gram-negative bacteria; synergy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Time-kill curves of antimicrobial peptide AA230 against (a) Escherichia coli ATCC (American Type Culture Collection); (b) Escherichia coli ESBL (extended spectrum beta lactamase).
Figure 2
Figure 2
Time-kill curves of antimicrobial peptide AA230 against (a) Acinetobacter baumannii ATCC (American Type Culture Collection); (b) Acinetobacter baumannii RCH.
Figure 3
Figure 3
Time-kill curves of antimicrobial peptide AA230 against (a) Pseudomonas aeruginosa ATCC (American Type Culture Collection); (b) Pseudomonas aeruginosa clinical isolate.
Figure 4
Figure 4
Time-kill curves of EDTA (etlylenediaminetetraacetic acid) against (a) Escherichia coli ATCC (American Type Culture Collection); (b) Escherichia coli ESBL (extended spectrum beta lactamase).
Figure 5
Figure 5
Time-kill curves of EDTA against (a) Acinetobacter baumannii ATCC (American Type Culture Collection); (b) Acinetobacter baumannii RCH.
Figure 6
Figure 6
Time-kill curves of EDTA against (a) Pseudomonas aeruginosa ATCC; (b) Pseudomonas aeruginosa clinical isolate.
Figure 7
Figure 7
Time-kill curves of antimicrobial peptide AA230 and EDTA used alone and in combination against (a,b) Escherichia coli ATCC; (c,d) Escherichia coli ESBL.
Figure 7
Figure 7
Time-kill curves of antimicrobial peptide AA230 and EDTA used alone and in combination against (a,b) Escherichia coli ATCC; (c,d) Escherichia coli ESBL.
Figure 8
Figure 8
Time-kill curves of antimicrobial peptide AA230 and EDTA used alone and in combination against (a,b) Acinetobacter baumannii ATCC; (c,d) Acinetobacter baumannii RCH.
Figure 8
Figure 8
Time-kill curves of antimicrobial peptide AA230 and EDTA used alone and in combination against (a,b) Acinetobacter baumannii ATCC; (c,d) Acinetobacter baumannii RCH.
Figure 9
Figure 9
Time-kill curves of antimicrobial peptide AA230 and EDTA used alone and in combination against (a) Pseudomonas aeruginosa ATCC; (b,c) Pseudomonas aeruginosa clinical isolate.
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