Chitosan-coated carboxylic acids show antimicrobial activity against antibiotic-resistant Gram-negative and positive pathogens

Abstract

Antibiotic resistance in bacteria is suggested to be the greatest risk to human health, but new agents are not being brought to market as the rapid evolution of resistance to them means that drug development costs cannot be recouped. Fatty acids have been proposed as a new generation of antibiotics, but toxicity and poor absorption has meant that their use has been impractical in the past. Chitosan has been used widely to encapsulate other agents as nanoparticles, but has not been used with fatty acids. Here we show that chitosan can be modified to direct fatty acids towards Gram-positive or negative bacteria so that they exert antimicrobial effects. We show that fatty acids work as effective antibiotics in vitro and in vivo, with activity against extremely drug resistant pathogens. Bacteria exposed to them do not develop resistance to these agents, and they are not toxic to mammalian cells. Activity was seen against salmonellosis and C. difficile infection in animal models. Our results demonstrate that fatty acids formulated as chitosan nanoparticles are effective antibiotics, and can be used for a long period of time without resistance developing. This suggests that the usage of fatty acids coated in this manner could be sold in sufficient quantities to recoup its development costs, overcoming this barrier. These agents would form a new class of antibiotics, with the novel property of lack of bacterial resistance.