Highly Potent Cationic Chitosan Derivatives Coupled to Antimicrobial Peptide Dendrimers to Combat Pseudomonas Aeruginosa.

The burden of bacterial wound infections has considerably increased due to antibiotic resistance to most of the currently available antimicrobial drugs. Herein, we report for the first time a chemical coupling of two cationic N-aryl (pyridyl and aminocinnamyl) chitosan derivatives to antimicrobial peptide dendrimers (AMPDs) of different generations (first, second and third) via thioether-haloacetyl reaction. The new chitosan-AMPD conjugates showed high selectivity by killing Pseudomonas aeruginosa and very low toxicity towards mammalian cells, as well as extremely low hemolysis to red blood cells. Electron microscopy revealed that the new chitosan derivatives coupled to AMPD destroyed both the inner and outer membranes of Gram-negative P. aeruginosa. Moreover, chitosan-AMPD conjugates showed synergetic effects within extremely low concentrations. The new chitosan-AMPD conjugates can be used as potent antimicrobial therapeutic agents, to eradicate pathogens such as those present in acute and chronic infected wounds. This article is protected by copyright. All rights reserved.