The increased emergence of drug resistant bacteria is one of the most serious problems in the modern medicine, and although new drugs are constantly being sought, the pace of development is slow compared to the evolution and spread of multidrug resistant species. In this study, the efficacy of the commercially available antibiotics (e.g. vancomycin and gentamicin) was synergistically enhanced by the enzymatic disruption of bacterial quorum sensing (QS) and ultrasound assisted nanotransformation of the antibacterial agents. The generated hybrid nano-antibacterials were deposited on silicone material in a Layer-by-Layer fashion. These nanocoatings disrupted bacterial QS signaling in reporter Chromobacterium violaceum and attenuated the virulence of P. aeruginosa, as demonstrated by the decrease of violacein, pyocyanin and alkaline protease production. Moreover, the multilayers eradicated Pseudomonas aeruginosa planktonic cells and inhibited up to 80 % the bacterium biofilm growth, without affecting the viability of human fibroblasts. Our results demonstrated that the hybrid nano-antibacterials, with complimentary modes of action, might be valuable alternatives to control drug-resistant biofilm occurrence on medical devices at reduced antibiotic dosages.
Bacteria-mediated diseases are a global healthcare concern due to the development and spread of antibiotic resistant strains. Cationic compounds are considered membrane active biocidal agents having a great potential to control bacterial infections, while limiting the emergence of drug resistance. Herein, the versatility and simplicity of the Layer-by- Layer (LbL) technique was used to functionalize polymer nanoparticles with antibacterial aminocellulose conjugate in a multilayer fashion. Stable polyelectrolyte-decorated particles with an average size of 250 nm and zeta potential of ± 40 mV were developed after five LbL assembly cycles. The antibacterial activity of these particles against Gram- positive Staphylococcus aureus and Gram-negative Escherichia coli increased significantly when the polycationic aminocellulose was applied as an uppermost layer. The large number of amino groups available on the particles surface improved the interaction with bacterial membrane phospholipids leading to membrane disturbance as was confirmed by Langmuir monolayer. The biopolymer decorated NPs were also able to inhibit the drug resistant biofilm formation, without affecting the human cells viability and therefore are promising alternatives for controlling bacterial infections occurrence.
Bacteriamediated diseases are global healthcare concern due to the accelerated emergence and spread of drug resistant bacterial strains. Cationic compounds are considered membrane active biocidal agents having a great potential to control bacterial infections while limiting the emergence of drug resistance. Herein, the versatility and simplicity of the LayerbyLayer (LbL) technique was used to functionalize poly (methyl vinyl ethercomaleic anhydride) nanoparticles with a highly antibacterial aminocellulose conjugate in a multilayer fashion. The assembly of cationic bearing aminocellulose with negatively charged hyaluronic acid on the particles surface was confirmed by the alternations of their surface charge and size after each deposition step. Stable polyelectrolyte decorated particles with an average size of 600 nm and zeta potential of ± 40 mV were developed after five LbL assembly cycles. The antibacterial properties of these particles against S. aureus were significantly improved when the polycationic aminocellulose was applied as a top layer. The large number of amino groups available on the particles surface allows for the interaction with intrinsically anionic bacterial cell wall leading to irreparable membrane damage and complete eradication of S. aureus after 24 h treatment, while the hyaluronic acid improve their biocompatibility. This specific mechanism of action is believed to diminish the possibility for selection of new resistant strains and is a great promise in controlling bacterial contamination