Antimicrobial Polymers: The Potential Replacement of Existing Antibiotics?

Abstract

Antimicrobial resistance is now considered a major global challenge; compromising medical advancements and our ability to treat infectious disease. Increased antimicrobial resistance has resulted in increased morbidity and mortality due to infectious diseases worldwide. The lack of discovery of novel compounds from natural products or new classes of antimicrobials, encouraged us to recycle discontinued antimicrobials that were previously removed from routine use due to their toxicity, e.g., colistin. Since the discovery of new classes of compounds is extremely expensive and has very little success, one strategy to overcome this issue could be the application of synthetic compounds that possess antimicrobial activities. Polymers with innate antimicrobial properties or that have the ability to be conjugated with other antimicrobial compounds create the possibility for replacement of antimicrobials either for the direct application as medicine or implanted on medical devices to control infection. Here, we provide the latest update on research related to antimicrobial polymers in the context of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. We summarise polymer subgroups: compounds containing natural peptides, halogens, phosphor and sulfo derivatives and phenol and benzoic derivatives, organometalic polymers, metal nanoparticles incorporated into polymeric carriers, dendrimers and polymer-based guanidine. We intend to enhance understanding in the field and promote further work on the development of polymer based antimicrobial compounds.

Keywords: ESKAPE pathogens; antimicrobial polymers; antimicrobial resistance.

Figure 1

The estimated number of deaths at every continent in 2050 attributed to antimicrobial resistance (AMR). Image adapted from [2].

Figure 2

The structural similarities between antimicrobial polymers and antimicrobial peptides. Image was adapted with permission from [53].

Figure 3

The proposed mechanism of bacterial killing activities by antimicrobial peptides. Image was adapted with permission from [69].

Figure 4

Chlorine-containing polymer.

Figure 5

Polymer-containing phosphor-derivatives.

Figure 6

Polyacrynitrilbenzaldehyde.

Figure 7

Schematic representation of the electrochemical deposition process and immobilization of bone morphology protein-2 (BMP-2_ on HA coatings on a Ti metal surface). Image was adapted with permission from [97].

Figure 8

The physical structure of a dendrimer.

Figure 9

Examples of common dendrimers for biological application.

Figure 10

(a) The guanidine structure (b) The polyhexamethylene biguanide (PHMB) structure. PHMB is a cationic polymer of repeating hexamethylene biguanide groups, with n average = 10–12 (n is the number of structural unit repeats) and molecular weight (mw) 3025 g/mol.

Figure 11

Intracellular localization and bactericidal activities of PHMB against intracellular methicillin-resistant S. aureus (MRSA). Colocalization of fluorescence-tagged PHMB (PHMB-FITC) with intracellular S. aureus strain EMRSA-15 in keratinocytes. Keratinocytes were infected with EMRSA-15 followed by treatment with PHMB-FITC (green). Keratinocytes were labelled with DAPI (blue) for keratinocytes and EMRSA-15 nuclei staining and WGA (red) for keratinocyte membrane stain. Upper panels are images of infected cells and merged images. Lower panels are enlarged images that clearly show colocalization between PHMB-FITC (green) and EMRSA-15 (blue). White scale bar is 25 μm. Image is reprinted from [22].