New perspectives for natural antimicrobial peptides: application as antinflammatory drugs in a murine model

Abstract

BackgroundAntimicrobial peptides (AMPs) are an ancient group of defense molecules. AMPs are widely distributed in nature (being present in mammals, birds, amphibians, insects, plants, and microorganisms). They display bactericidal as well as immunomodulatory properties. The aim of this study was to investigate the antimicrobial and anti-inflammatory activities of a combination of two AMPs (temporin B and the royal jellein I) against Staphylococcus epidermidis.ResultsThe temporin B (TB-KK) and the royal jelleins I, II, III chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C), were tested for their activity against 10 different Staphylococcus epidermidis strains, alone and in combination. Of the three royal jelleins, RJI-C showed the highest activity. Moreover, the combination of RJI-C and TB-KK (MIX) displayed synergistic activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-α and IFN-γ to the same extent as acetylsalicylic acid. In vivo, the MIX sterilized mice infected with Staphylococcus epidermidis in eleven days and inhibited the expression of genes encoding the prostaglandin-endoperoxide synthase 2 (COX-2) and CD64, two important parameters of inflammation.ConclusionThe study shows that the MIX – a combination of two naturally occurring peptides - displays both antimicrobial and anti-inflammatory activities.

Clavanin bacterial sepsis control using a novel methacrylate nanocarrier

“…Nanostructures were 80 and 230 nm in diameter, by DLS. 22 Moreover, Fontana et al 39 presented an interesting study using amoxicillinloaded polyethylcyanoacrylate nanoparticles with added polyethyleneglycol (PEG), measuring 220-320 nm. Turos et al 14 proposed penicillin-bonded polyacrylate nanoparticles with 25-40 nm.…”

“…EUDRAGIT ® L 100-55 and EUDRAGIT ® RS 30 D are methacrylate polymers and can present inflammatory effects on the human system when at higher concentrations. 22 Despite 57,61 In fact, nanostructures can provide some antimicrobial activity against lower concentrations of bacteria by polymer-bacterial membrane interactions 21,30 or induce immune response activity in the host system. 57 However, these nanostructures were not able to provide antimicrobial activity at higher bacterial concentrations, as shown in in-vivo analysis, and cannot show effective modulation activity in response to the excessive immune response caused by SIRS.…”

“…17,18 These polymers present 99% purity, 17,19 simplifying the nanostructuration protocol based on hydrophobicity and higher encapsulation efficiency. 10,17,[19][20][21][22] Polymer hydrophobicity allows its solubilization on acetone 95% and ethanol 5% solution, and further peptide coupling occurs after water addition, due to amphipathic properties of clavanin used here. Moreover, release assays showed a higher stability of methacrylate nanostructures in water, as discussed above.…”

Immunomodulatory effects of anti-microbial peptides

“…The best example of the cooperation between microbiological and immunological effects came when a hyaluronic acid-binding peptide, preventing staphylococcal infections, was considered an immunological therapeutic agent rather than an antibiotic in spite of its sequence demonstrating striking similarity to cationic AMP [28]. Later research on AMPs was extended to activation of macrophage activity [29] and upregulation of anti-inflammatory cytokine production [30]. Because the true role of cationic peptides is to enhance chemotaxis or growth factor activation, it was suggested that these peptides were misclassified as anti-microbials [31].…”

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

“…1 Antimicrobial peptides or proteins represent a source of "natural antibiotics", and have been found in a wide range of organisms (bacteria, plants, insects, amphibians, and mammals) where they play an important role in defense. [2][3][4][5][6] Lactoferrin (LF) is an antimicrobial protein that was first identified in bovine milk and later in neutrophil granules, as well as in mucosal secretions, such as saliva and the nasal and bronchial secretions of various mammalian species, including man, goat, horse, and rodents. 7,8 LF is a nonheme glycoprotein with a molecular weight of about 80 kDa and is a part of the transferrin protein family, so is one of the proteins capable of binding and transferrin Fe 3+ ions in serum.…”