BackgroundCeragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity.ResultsOur studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface.ConclusionOur results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.

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Growing antibiotic resistance among pathogenic microorganisms is one of the most challenging problems. Often, a single mutation in a bacterial cell leads to the formation of a new drug resistance mechanism. The ceragenins are a novel class of antibiotic, offering great promise in future treatment of infections. These cationic antimicrobial lipids are net positively charged cholic acid derivates that are electrostatically attracted to the negatively charged membranes of bacteria, certain viruses, fungi, and protozoa. After membrane insertion, they interfere with membrane organisation, resulting in membrane dysfunction and cell death. This review focuses on the broad spectrum of antibacterial activity of ceragenins, and their potential to become a new group of antibiotics for prevention and treatment of infections, especially those caused by multidrug-resistant bacteria. StreszczenieStale narastająca oporność bakterii na antybiotyki jest jednym z najtrudniejszych problemów. Często pojedyncza mutacja w komórce bakteryjnej prowadzi do powstania i rozwoju nowego mechanizmu, nadającego bakteriom oporność na antybiotyki. Cerageniny (pochodne kwasu cholowego) są analogami naturalnych kationowych peptydów przeciwbakteryjnych oferujących nowe możliwości w leczeniu infekcji bakteryjnych. Mają one dodatni ładunek powierzchniowy, dzięki czemu oddziałują elektrostatycznie z negatywnie naładowaną powierzchnią bakterii, wirusów, grzybów i pierwotniaków. Po insercji w strukturę lipidową błony mikroorganizmów zaburzają jej funkcję, co w efekcie prowadzi do śmierci komórki. W niniejszej pracy przedstawiono szerokie spektrum aktywności przeciwdrobnoustrojowej ceragenin i ich potencjał w zwalczaniu infekcji, w szczególności powodowanych przez wielooporne szczepy bakteryjne.

Background: Ceragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity. Results: Our studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface. Conclusion: Our results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.