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

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.

Exploration of Antibiotic Activity of Aminoglycosides, in Particular Ribostamycin Alone and in Combination With Ethylenediaminetetraacetic Acid Against Pathogenic Bacteria

“…EDTA, a small molecule metal ion chelator, has been reported as a highly effective additive that increases bacterial membrane permeability and improves the efficacy of antibiotics (Brown and Richards, 1965;Leive, 1965;Sparks et al, 1994;Lambert et al, 2004;Martin-Visscher et al, 2011;Lebeaux et al, 2014). EDTA has been effectively used in combination with many antibiotics, including gentamicin and amikacin, where a synergistic activity with these antibiotics has been observed (Lambert et al, 2004;Lebeaux et al, 2015;Umerska et al, 2018;Khazandi et al, 2019). Based on literature precedent, we hypothesized that the efficacy of ribostamycin against resistant bacteria can be improved via a combination treatment with an adjuvant, such as EDTA.…”

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy

“…Most blood samples are collected in tubes (vacutainers) containing an anticoagulant to prevent blood clotting and it is known that the presence of an anticoagulant can affect AMP activity. For example, EDTA and citrate are known to enhance the efficacy of some AMP as they can chelate divalent cations which are inhibitory to the activity of a number of AMP (Wei and Bobek, 2005 ; Walkenhorst et al, 2014 ; Maisetta et al, 2017 ; Umerska et al, 2018 ; Grassi et al, 2019 ) and EDTA and heparin can inactivate proteases found in blood, including metalloproteases (EDTA), thrombin and Factor Xa (heparin) that may prevent AMP hydrolysis (Bowen and Remaley, 2014 ; Bottger et al, 2017 ; Rawlings et al, 2018 ).…”

“…However, this is not necessarily as simple as it appears. A number of protease inhibitors, including EDTA and citrate, can enhance AMP activity by chelation of metal ions, or by other unknown mechanisms, and this activity would need to be determined prior to their use in AST (Wei and Bobek, 2005 ; Walkenhorst et al, 2014 ; Maisetta et al, 2017 ; Umerska et al, 2018 ; Grassi et al, 2019 ).…”

Penapisan Actinobacteria Akuatik Penghasil Antibakteri Dari Ikan Bandeng (Chanos chanos) dan Belanak (Mugil cephalus) dengan Metode Double-Layer Diffusion

“…Aktivitas antibakteri yang tinggi pada bakteri uji Gram-negatif diduga disebabkan karena senyawa aktif yang terkandung dalam ekstrak kasar mampu melakukan pengikatan langsung dengan fosfolipid sehingga jalur transportasi fosfolipid (phospholipid transportation pathway) antara kedua membran menjadi terputus. Hal ini mengakibatkan terjadinya disregulasi komposisi membran dan mengganggu integritas membran (Umerska et al, 2018). Selain mekanisme tersebut, senyawa aktif yang terkandung dalam ekstrak kasar juga diduga memiliki berat molekul kurang dari 600 Da.…”