Université de Lorraine, CITHEFOR, F-54000 Nancy, France.
MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, F-49933 Angers, France.
Biomolecules. 2018 Oct 23;8(4):122. doi: 10.3390/biom8040122.
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 at 500⁻1000 µg/mL. Strains of were found to be more susceptible to EDTA than or . 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.
全球范围内标准抗生素耐药性的出现和新抗菌药物的缺乏，需要新的策略来治疗复杂感染。因此，本研究的目的是研究一种抗菌肽，arenicin-3 衍生物 AA230，以及乙二胺四乙酸（EDTA）以及这两种化合物联合对抗革兰氏阴性菌的抗菌活性。AA230 对所有研究的标准菌株和临床分离株均显示出很强的抗菌活性，最低抑菌浓度范围在 1 µg/mL 至 8 µg/mL 之间。AA230 表现出杀菌作用模式。EDTA 在 500-1000 µg/mL 时抑制 的生长。发现与 或 相比， 对 EDTA 更敏感。AA230 和 EDTA 的抗菌作用均独立于抗生素耐药模式。棋盘滴定法显示 AA230 和 EDTA 联合使用时没有协同活性。在时间杀伤研究中，检测到 AA230 和 EDTA 对所有测试菌株均存在显著协同相互作用。添加 EDTA 可使 AA230 的剂量降低 2-4 倍。总之，AA230 可能在治疗革兰氏阴性菌引起的感染方面具有应用潜力，其作用可以通过 EDTA 增强。
