Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its ability, in combination with EDTA, to eradicate Staphylococcus epidermidis biofilms on silicone catheters

Abstract

In search of new antimicrobials with anti-biofilm potential, in the present study activity of the frog-skin derived antimicrobial peptide temporin 1Tb (TB) against Staphylococcus epidermidis biofilms was investigated. A striking ability of TB to kill both forming and mature S. epidermidis biofilms was observed, especially when the peptide was combined with cysteine or EDTA, respectively. Kinetics studies demonstrated that the combination TB/EDTA was active against mature biofilms already after 2-4-h exposure. A double 4-h exposure of biofilms to TB/EDTA further increased the therapeutic potential of the same combination. Of note, TB/EDTA was able to eradicate S. epidermidis biofilms formed in vitro on silicone catheters. At eradicating concentrations, TB/EDTA did not cause hemolysis of human erythrocytes. The results shed light on the anti-biofilm properties of TB and suggest a possible application of the peptide in the lock therapy of catheters infected with S. epidermidis.

Analogs of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

“…The possibility to improve the activity of TB analogs against preformed biofilms of S. aureus and P. aeruginosa was investigated combining the peptides with EDTA, a chelating agent previously reported to enhance the antibiofilm properties of TB (Maisetta et al, 2016). Indeed, the ability of EDTA to establish strong complexes with divalent cations essential for matrix stability could produce a matrix-disaggregating effect and promote the accessibility of peptides to biofilm-forming cells.…”

“…Thus, the use of AMPs in combination with compounds able to disaggregate the extracellular matrix could represent a promising strategy to increase their antibiofilm activity and therapeutic potential. In this regard, the chelator EDTA has been shown to reduce the structural integrity of the biofilm of several bacterial species by forming strong complexes with divalent cations (magnesium, calcium, iron) essential for matrix stability (Percival et al, 2005; Banin et al, 2006; Cavaliere et al, 2014; Maisetta et al, 2016). Herein, we combined TB analogs with EDTA in order to improve their efficacy against preformed biofilms of S. aureus and P. aeruginosa .…”

“…The peptide has previously demonstrated a fast and potent bactericidal action particularly against Gram-positive bacterial species, such as multidrug-resistant nosocomial strains of Staphylococcus aureus and Enterococcus faecium (Mangoni et al, 2008). The antibiofilm properties of TB have been also investigated showing high activity against both forming and mature biofilms of Staphylococcus epidermidis , especially when the peptide was used in combination with EDTA (Maisetta et al, 2016). Interestingly, it has been recently reported that the peptide is able to penetrate eukaryotic cells, kill intracellular S. aureus and promote wound-healing, further important properties in view of a therapeutic development (Di Grazia et al, 2014).…”

Staphylococcus aureusextracellular vesicles (EVs): surface-binding antagonists of biofilm formation

“…EDTA acts as a chelator and is reported to remove biofilms of S. aureus , S. epidermidis and P. aeruginosa . 65-69 For P. aeruginosa , EDTA appears to act by chelating divalent cations (calcium, magnesium, iron) within the biofilm, leading to its dispersal due to loss of electrostatic interactions that contribute to its stability 70, 71 . For S. aureus , EDTA was found to act by inhibiting interactions between this pathogen and the surface 72 .…”

Urinary Catheter Coating Modifications: The Race against Catheter-Associated Infections

“…Combinatorial therapies have shown positive results in vitro, examples of these combinations are: (1) silver with several antimicrobial or antifouling compounds such as norfloxacin [151], amikacin [82], nitrofurantoin [82], chlorhexidine [152]; phosphorylcholines [75]; hydroxyapatite [76]; or even plasma [153]; (2) polyzwitterions with cellobiose dehydrogenase [45]; (3) antimicrobial peptide temporin 1Tb with EDTA [154]; (4) chlorhexidine with gentian violet against Candida spp. [107], and (5) bacteriophage with a pre-established biofilm of non-pathogenic E. coli HU2117 on catheter against P. aeruginosa [155].…”