Peptidomimetic Polyurethanes Inhibit Bacterial Biofilm Formation and Disrupt Surface Established Biofilms

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 1000-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 Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, all of which show tolerance to the conventional antibiotics polymyxin B and ciprofloxacin. Furthermore, while these polyurethanes show poor antimicrobial activity against planktonic bacteria, they prevent surface attachment and stimulate bacterial surface motility to inhibit biofilm formation of both Gram-positive and Gram-negative bacteria at subinhibitory 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.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

“…4 E) [ 167 ]. Covalently introducing cationic and hydrophobic amino acids into a PU can prevent surface attachment of both Gram-positive and Gram-negative bacteria at subinhibitory concentrations and disrupt their biofilm formation without toxicity to mammalian cells [ 170 ]. In another approach, chitooligosaccharide (COS), a low-molecular-weight chitosan with antibacterial properties, was grafted onto the PU surface through the self-polymerization of dopamine [ 165 ].…”

Surface Characterization and Anti-Biofilm Effectiveness of Hybrid Films of Polyurethane Functionalized with Saponite and Phloxine B

“…The surfaces of PU composites (PUC) often exhibit antimicrobial properties, which have been described in several papers [10,11]. In the case of composites with organoclays (OC), the antimicrobial effect of the surface was related to the amount and type of alkylammonium cations used in the silicate modification.…”

“…OCs are characterized by the ability to adsorb various bioactive molecules and thus form ternary systems with even better antimicrobial properties. In some cases, the effects of such modified surfaces have also been demonstrated against otherwise resistant biofilm-forming pathogens [10,11]. In a few cases, PUCs were prepared that could, in a controllable manner, release biologically active molecules into the environment, thus providing the potential for the elimination of the initial stages of biofilm formation.…”

Peptidomimetics as Potential Anti-Virulence Drugs Against Resistant Bacterial Pathogens

“…The blockage of this initial step could impair biofilm establishment. Four synthetic polyurethanes (mLys/mPhe, mLys/mAla, mArg/mAla, and mArg/mPhe) that mimic anti-biofilm peptides were reported ( Table 2 ; Vishwakarma et al, 2021 ). Each synthetic polyurethane consisted of charged and hydrophobic pendant groups with a charge-to-hydrophobicity ratio of 60/40.…”