Peptidomimetic Polyurethanes Disrupt Surface Established Bacterial Biofilms and Prevent Biofilm Formation

Abstract

Over 80% of all chronic bacterial infections in humans are associated with biofilms, which are surface-associated bacterial communities encased within a secreted exopolysaccharide matrix that can provide resistance to environmental and chemical insults. Biofilm formation triggers broad adaptive changes in the bacteria, allowing them to be almost a thousand-fold more resistant to conventional antibiotic treatments and host immune responses. The failure of antibiotics to eliminate biofilms leads to persistent chronic infections and can promote the development of antibiotic-resistant strains. Therefore, there is an urgent need to develop agents that effectively prevent biofilm formation and eradicate established biofilms. Herein, we present water-soluble synthetic peptidomimetic polyurethanes that can disrupt surface established biofilms of <i>Pseudomonas aeruginosa, Staphylococcus aureus, </i>and <i>Escherichia coli</i>, all of which show tolerance to the conventional antibiotics polymyxin B and ciprofloxacin. Furthermore, these polyurethanes prevent bacterial attachment and stimulate bacterial surface motility to inhibit biofilm formation of both Gram-positive and Gram-negative bacteria at sub-inhibitory concentrations, without being toxic to mammalian cells. Our results show that these polyurethanes show promise as a platform for the development of therapeutics that target biofilms and modulate surface interactions of bacteria for the treatment of chronic biofilm-associated infections and as antibiofilm agents.

Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus

“…In response to this obstacle, attention has been drawn to the development of antimicrobial peptides (AMPs) as a novel class of antibiotics [ 25 , 26 ]. AMPs that play important roles in the innate human immune system have attracted special attention as an alternative to conventional antibiotics to prevent and treat bacterial infections, especially for treating biofilm-associated infectious diseases [ 27 , 28 , 29 , 30 ], owing to their broad spectrum activity, low incidence of resistance development, and ability to kill stationary phase “persister” cells through a membrane-active mode of action [ 31 ]. Confronting increasingly serious drug-resistant bacteria infections, especially biofilm infections and persister bacteria infections, AMPs are considered to be the most ideal solution.…”