Activity of Temporin A and Short Lipopeptides Combined with Gentamicin against Biofilm Formed by Staphylococcus aureus and Pseudomonas aeruginosa

Abstract

The formation of biofilms on biomaterials causes biofilm-associated infections. Available treatments often fail to fight the microorganisms in the biofilm, creating serious risks for patient well-being and life. Due to their significant antibiofilm activities, antimicrobial peptides are being intensively investigated in this regard. A promising approach is a combination therapy that aims to increase the efficacy and broaden the spectrum of antibiotics. The main goal of this study was to evaluate the antimicrobial efficacy of temporin A and the short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 in combination with gentamicin against biofilm formed by Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Peptides were synthesized with solid-phase temperature-assisted synthesis methodology. The minimum inhibitory concentrations (MICs), fractional inhibitory concentrations (FICs), minimum biofilm eradication concentrations (MBECs), and the influence of combinations of compounds with gentamicin on bacterial biofilm were determined for reference strains of SA (ATCC 25923) and PA (ATCC 9027). The peptides exhibited significant potential to enhance the antibacterial activity of gentamicin against SA biofilm, but there was no synergy in activity against planktonic cells. The antibiotic applied alone demonstrated strong activity against planktonic cells and poor effectiveness against SA biofilm. Biofilm formed by PA was much more sensitive to gentamicin, but some positive influences of supplementation with peptides were noticed. The results of the performed experiments suggest that the potential application of peptides as adjuvant agents in the treatment of biofilm-associated infections should be studied further.

Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers

“…Moreover, their susceptibility depends on the biofilm maturity and the antibiotic used [ 98 ]. It was found that the antibiofilm activity of antibiotics (e.g., daptomycin, gentamicin) can be potentiated (synergistic effect) through supplementation with cationic antimicrobial peptides and lipopeptides [ 99 , 100 ]. Therefore, further studies should be extended to examine antibiofilm activity of gemini surfactants combined with antibiotics.…”

The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy Against Staphylococcus aureus

“…Temporins were initially isolated from the European red frog Rana temporaria , and nowadays they represent one of the largest groups of amphibian AMPs (more than 100 members) [ 15 , 16 ] and are among the shortest AMPs (only 10-13 residues) present in nature to date. While some isoforms (i.e., temporin A, (TA [FLPLIGRVLSGIL-NH 2 ]); temporin B (TB [LLPIVGNLLKSLL-NH 2 ]); temporin L (TL [FVQWFSKFLGRIL-NH 2 ]) of this family have already been characterized for their antimicrobial and cytotoxic properties [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], very little is known about the antimicrobial potential of temporin G (TG [FFPVIGRILNGIL-NH 2 ]) [ 25 ], which was isolated from the same frog specimen, especially against the bacterial biofilm phenotype. To the best of our knowledge, this is the first manuscript describing TG activity against preformed S. aureus biofilm as well as against persister cells.…”

Amyloidogenic Peptides: New Class of Antimicrobial Peptides with the Novel Mechanism of Activity

“…As a result of the series of experiments, the minimum inhibitory concentrations (MICs) of the modified peptides were determined against strains of pathogenic methicillin-resistant S. aureus (MRSA), S. aureus, and P. aeruginosa (Table 2) [35,36]. As follows from Table 2, we found that the antimicrobial effect of the same peptides against various pathogenic microorganisms is comparable to the MIC (~1-5 µM) of the commercial antibiotic gentamicin sulfate [116,117].…”