Antimicrobial polymers as synthetic mimics of host‐defense peptides

Abstract

Antibiotic-resistant bacteria 'superbugs' are an emerging threat to public health due to the decrease in effective antibiotics as well as the slowed pace of development of new antibiotics to replace those that become ineffective. The need for new antimicrobial agents is a well-documented issue relating to world health. Tremendous efforts have been given to developing compounds that not only show high efficacy, but also those that are less susceptible to resistance development in the bacteria. However, the development of newer, stronger antibiotics which can overcome these acquired resistances is still a scientific challenge because a new mode of antimicrobial action is likely required. To that end, amphiphilic, cationic polymers have emerged as a promising candidate for further development as an antimicrobial agent with decreased potential for resistance development. These polymers are designed to mimic naturally occurring host-defense antimicrobial peptides which act on bacterial cell walls or membranes. Antimicrobial-peptide mimetic polymers display antibacterial activity against a broad spectrum of bacteria including drug-resistant strains and are less susceptible to resistance development in bacteria. These polymers also showed selective activity to bacteria over mammalian cells. Antimicrobial polymers provide a new molecular framework for chemical modification and adaptation to tune their biological functions. The peptide-mimetic design of antimicrobial polymers will be versatile, generating a new generation of antibiotics toward implementation of polymers in biomedical applications.

Antimicrobial cationic polymers: from structural design to functional control

“…[65][66][67][68] By varying the specific structures of cationic groups and hydrophobic groups, the antimicrobial activity against particular microbes can be selectively enhanced as well. [69][70][71][72][73][74][75][76][77] It should be noted that the physical chemistry behind the globally amphiphilic antimicrobial cationic polymers needs to be studied furthermore for providing the guidelines for fabrication of antimicrobial materials with tailor-made structures and functions.…”

Engineering Microbial Physiology with Synthetic Polymers: Cationic Polymers Induce Biofilm Formation inVibrio choleraeand Downregulate the Expression of Virulence Genes

“…Having identified that P1 was able to sequester V. cholerae into clusters, we then evaluated the viability of the pathogen in the presence of this polymer. Cationic polymers are commonly reported as bactericidal materials, [8][9][10][11] although small changes in structure and dose can result in significant differences in activity and toxicity. This effect is often microbe specific, and in particular P1 has been reported to have a minimum inhibitory concentration of 10-25 μg/mL for Escherichia coli, 30 while showing no effect on V. harveyi's viability and growth at concentations as high as 500 μg/mL.…”

“…Not suprisingly, P1 compromised membrane integrity of the mammalian cells at the highest concentrations tested (≥ 50 μg/mL), in agreement with the reported toxicity of cationic materials. [8][9][10][11] However, we anticipated that this toxicity could be reduced following incubation with bacteria, as the cationic charge will not be exposed following interaction with the pathogen's negatively charged membrane. This was indeed the case when we evaluated the potential of this polymer to inhibit colonisation by V. cholerae of this intestinal epithelial cell line (Fig.…”

“…In particular novel approaches that can replace or enhance current antimicrobials are highly desired. [3][4][5] Polymeric materials have often been postulated as alternatives in these areas, either as delivery vehicles for antimicrobials, 6,7 or as novel antimicrobial polymers, [8][9][10][11] and materials that can interfere with microbial adhesion. [12][13][14][15] Polymeric materials are especially attractive in these applications because of their multivalency, ease of manufacturing and the potential to precisely control polymer length and composition.…”

Exploring Novel Polymer Coatings for Antimicrobial Applications

“…Spacers are the sections connecting the cationic group to the polymer backbone, functioning to extend the antibiotic groups into the membrane of cells, as described by the "snorkelling effect". 154 Palermo et al 133 found that longer spacers can significantly increase the antibiotic performance and haemolytic activity, which may be related to the rise in the hydrophobicity of the polymer. Molecular dynamics simulations confirmed the formation of facially amphiphilic structures adopted by the antibiotic polymers and showed that elongated spacers positioned the polymer backbone closer to the lipid core of the cell membrane, consistent with the description of the "snorkelling effect".…”