<p>Synergistic Anti-Staphylococcal Activity Of Niosomal Recombinant Lysostaphin-LL-37</p>

Abstract

PurposeStaphylococcus aureus is the most common persistent pathogen in humans, so development of new formulations to combat pathogen invasion is quite necessary.MethodsIn the current study, for the first time, the synergistic activity of recombinant lysostaphin and LL-37 peptide was studied against S. aureus. Moreover, different niosomal formulations of the peptide and protein were prepared and analyzed in terms of size, shape, zeta potential, and entrapment efficiency. Also, a long-term antibacterial activity of the best niosomal formulation and free forms was measured against S. aureus in vitro.ResultsThe optimal niosomal formulation was obtained by mixing the surfactants (span60 and tween60; 2:1 w/w), cholesterol, and dicetylphosphate at a ratio of 47:47:6, respectively. They showed uniform spherical shapes with the size of 565 and 325 nm for lysostaphin and LL-37, respectively. This formulation showed high entrapment efficiency for the peptide, protein, and a slow-release profile over time. Release kinetic was best fitted by Higuchi model indicating a diffusion-based release of the drugs. The lysostaphin/LL-37 niosomal formulation synergistically inhibited growth of S. aureus for up to 72 hours. However, the same amounts of free forms of both anti-microbial agents could not hold the anti-microbial effect and growth was seen in the following 72 hours. Cytotoxicity assay specified that lysostaphin/LL-37 niosomal combination had no deleterious effect on normal fibroblast cells at effective antimicrobial concentrations.ConclusionThis study indicated that the use of lysostaphin in combination with LL-37, either in niosomal or free forms, synergistically inhibited growth of S. aureus in vitro. In addition, niosomal preparation of antimicrobial agents could provide a long-term protection against bacterial infections.

Reduced Growth of Staphylococcus aureus Under High Glucose Conditions Is Associated With Decreased Pentaglycine Expression

“…Lysostaphin shows rapid bactericidal activity against methicillin-susceptible and -resistant strains of S. aureus, with minimum inhibitory concentrations (MICs) ranging from 0.03 to 2 µg/mL, as determined using an agar dilution assay (Yang et al, 2007). Recent studies have reported that lysostaphin combined with other agents, such as LL-37 peptide, liposomal vancomycin, and nisin, are effective against S. aureus infection (Ceotto-Vigoder et al, 2016;Hajiahmadi et al, 2019;Sadeghi et al, 2019). However, the MIC values of lysostaphin are greatly increased by serial subculture (Gutierrez et al, 2020).…”

Encapsulation and Characterization of Meropenem in Niosome Nanoparticles and Inhibitory Effects of Antibiofilm and Antibacterial on Methicillin and Vancomycin Resistant Strains of Staphylococcus Aureus

“…Given that various cholesterol levels could result in various bilayers in formulations and impact bilayers' surface load, its amount was kept steady across all formulations. Therefore, the niosome membrane's strength and resistance to ultrasound waves were kept constant across all formulations by keeping the cholesterol constant which resulted in more uniform vesicles in terms of size (35). On the other hand, various surfactant combinations resulted in nanostructures with various morphological features (36).…”

Niosome‐encapsulated tobramycin reduced antibiotic resistance and enhanced antibacterial activity against multidrug‐resistant clinical strains of Pseudomonas aeruginosa

“…According to the results, the decrease in cholesterol levels affects the size of the nanovesicle, which is consistent with previous studies 38 . This could be associated to the effect of cholesterol amount on the rigidity of niosomes; high cholesterol level, by increasing niosome membrane rigidity and resistance, decreases the effect of ultrasound waves and results in a larger vesicle 34,39 . Moreover, the diameter of the nanoparticle is one of the most important factors that affect the efficiency of drug encapsulation and release in drug delivery systems.…”