Susceptibility of microbial cells to the modified PIP2-binding sequence of gelsolin anchored on the surface of magnetic nanoparticles

Abstract

Background: Magnetic nanoparticles (MNPs) are characterized by unique physicochemical and biological properties that allow their employment as highly biocompatible drug carriers. Gelsolin (GSN) is a multifunctional actin-binding protein involved in cytoskeleton remodeling and free circulating actin sequestering. It was reported that a gelsolin derived phosphoinositide binding domain GSN 160-169, (PBP10 peptide) coupled with rhodamine B, exerts strong bactericidal activity. Results: In this study, we synthesized a new antibacterial and antifungal nanosystem composed of MNPs and a PBP10 peptide attached to the surface. The physicochemical properties of these nanosystems were analyzed by spectroscopy, calorimetry, electron microscopy, and X-ray studies. Using luminescence based techniques and a standard killing assay against representative strains of Gram-positive (Staphylococcus aureus MRSA Xen 30) and Gram-negative (Pseudomonas aeruginosa Xen 5) bacteria and against fungal cells (Candida spp.) we demonstrated that magnetic nanoparticles significantly enhance the effect of PBP10 peptides through a membrane-based mode of action, involving attachment and interaction with cell wall components, disruption of microbial membrane and increased uptake of peptide. Our results also indicate that treatment of both planktonic and biofilm forms of pathogens by PBP10-based nanosystems is more effective than therapy with either of these agents alone. Conclusions: The results show that magnetic nanoparticles enhance the antimicrobial activity of the phosphoinositide-binding domain of gelsolin, modulate its mode of action and strengthen the idea of its employment for developing the new treatment methods of infections.