Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glucosamine-Functionalized Star Polymers

Abstract

The development of novel reagents and antibiotics for combating multidrug resistance bacteria has received significant attention in recent years. In this study, new antimicrobial star polymers (14-26 nm in diameter) that consist of mixtures of polylysine and glycopolymer arms were developed and were shown to possess antimicrobial efficacy toward Gram positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (with MIC values as low as 16 μg mL(-1)) while being non-hemolytic (HC50 > 10,000 μg mL(-1)) and exhibit excellent mammalian cell biocompatibility. Structure function analysis indicated that the antimicrobial activity and mammalian cell biocompatibility of the star nanoparticles could be optimized by modifying the molar ratio of polylysine to glycopolymers arms. The technology described herein thus represents an innovative approach that could be used to fight deadly infectious diseases.

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

“…The trend is similar to that previously reported for the linear polylysine, albeit with lower MIC values overall. 22 This discrepancy is probably due to the different bacterial strains used. In general, all of the glycopolymer-polypeptide conjugates exhibit higher MIC values than P(Lys).…”

“…Up to 10 000 µg mL −1 of linear polylysine prepared by the NCA ROP technique was non-hemolytic toward human erythrocytes. 22 It appears that the absence of a hydrophobic domain might contribute to the remarkable hemocompatibility of the linear P(Lys) and glycopolymer-polypeptide conjugates, as hydrophobic groups are known to be responsible for inducing hemolytic activity.…”

“…20,21 For example, glucosamine was employed to functionalize star polymers comprising of antimicrobial polylysine, which resulted in dramatic improvement of cytocompatibility toward human aortic smooth muscle cells. 22 On the other hand, glycomaterials also display interesting characteristics in many biological recognition events, such as cell-cell adhesion and development of new tissues, and thus have potential applications in targeted drug delivery, tissue engineering, and synthesis of biocompatible materials. 23,24 Micro-organisms exhibit preferential adhesion to specific substrates, and this characteristic is a plausible target in the design of new antimicrobial compounds.…”

Antimicrobial and Hemolytic Studies of a Series of Polycations Bearing Quaternary Ammonium Moieties: Structural and Topological Effects

“…In the USA alone, over 2 million people are infected with these strains and more than 23,000 die yearly for this reason [8]. In Europe more than 150,000 patients are affected by methicillin-resistant Staphylococcus aureus (MRSA) infections, which leads to costs of 380 million euros per year [9,10]. Hence, the demand for new antibiotics to combat resistant strains is currently very high.…”

Antimicrobial and Anti‐Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity

“…Thereafter, stock solutions of the nanoparticles (in PBS) were serially diluted in MHB. Equal volumes of the polymers (100 μL) were thereafter added to the diluted bacteria cultures (3 × 10 5 CFU mL –1 ) and incubated at 37 °C . After the incubation period, OD readings at 600 nm were determined spectrophotometrically (TECAN, Switzerland).…”