Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant against <em>Staphylococcus aureus</em>

Abstract

Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of S. aureus , independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%–62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against S. aureus , as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against S. aureus , including MRSA.

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

“…25 Recently, the MICs of plectasin derivatives against 14 studied strains was determined by Umerska et al and the MICs of AP138 varied 16-fold (range 0.125-4 µg/mL). 26 This is in good agreement with previously reported data showing that the antibacterial spectrum of AP138 includes staphylococci such as MRSA. 20 Garbacz et al reported that the MICs of AMPs for 215 isolates of SA from cystic fibrosis patients varied from 4 to 256 µg/mL.…”

Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity

“…Similar to our findings, loading into nanocarriers has been shown to affect the antibacterial activity of loaded compounds, such as antimicrobial peptides [ 38 , 39 ]. Interestingly, the employment of nanocarriers with antibacterial properties, such as monolaurin -LNCs, which showed potent activity against Staphylococcus aureus , resulted in synergistic interactions with peptides derived from plectasin [ 25 ], which is a promising strategy for other compounds such as antipsychotic drugs.…”

“…The drug contents were analyzed using an HPLC system previously described [ 25 ]. Briefly, standard solutions of the drugs (0.1–1000 μg/ml) were prepared in deionized water, and 20 μl of the standard or sample were injected into the SymmetryShield TM RP 18 5 μm 4.6x250 mm column (Waters, USA).…”

Antimicrobial peptides under clinical investigation

“…[79,99] β-sheet mixed secondary structure when they inhibit bacterial cell wall biosynthesis. [80] Novamycin (34, NP339) is an antifungal peptide being evaluated by Novabiotics. The 14-mer arginine cationic peptide induces membrane disruption of Aspergillus spp.…”

“…Both 40‐amino acid peptides have similar structural characteristics including amphipathic, macrocyclic, and disulfide bonds, except for the extent of the net positive charge. AP114 and AP138 also exhibit α‐helical and β‐sheet mixed secondary structure when they inhibit bacterial cell wall biosynthesis …”