Antimicrobial peptide polymers: no escape to ESKAPE pathogens-a review

Abstract

Antimicrobial resistance (AMR) is one of the significant clinical challenges and also an emerging area of concern arising from nosocomial infections of ESKAPE pathogens, which has been on the rise in both the developed and developing countries alike. These pathogens/superbugs can undergo rapid mutagenesis, which helps them to generate resistance against antimicrobials in addition to the patient's non-adherence to the antibiotic regimen. Sticking to the idea of a 'one-size-fits-all' approach has led to the inappropriate administration of antibiotics resulting in augmentation of antimicrobial resistance. Antimicrobial peptides (AMPs) are the natural host defense peptides that have gained attention in the field of AMR, and recently, synthetic AMPs are well studied to overcome the drawbacks of natural counterparts. This review deals with the novel techniques utilizing the bacteriolytic activity of natural AMPs. The effective localization of these peptides onto the negatively charged bacterial surface by using nanocarriers and structurally nanoengineered antimicrobial peptide polymers (SNAPPs) owing to its smaller size and better antimicrobial activity is also described here.

Keywords: Antimicrobial peptides; Antimicrobial resistance; ESKAPE pathogens; Nanostructured antimicrobial peptides; Structurally nanoengineered antimicrobial peptide polymers (SNAPPs).

Fig. 1

General mechanism of action of antimicrobial peptides; a represents attraction step where electrostatic bonding arises between negatively charged peptidoglycan layer of the bacterial cell membrane and amphiphilic polypeptide structure; b represents attachment step where the AMPs binds to Lipopolysaccharide (LPS) layer of Gram-negative cell wall and a teichoic acid layer of Gram-positive cell wall; c Represents the final peptide insertion step where following attachment the peptide forms a pore and thus disrupts the bacterial cell membrane

Fig. 2

a Barrel-stave model of pore formation by AMPs, the hydrophobic region marked by red color aligns itself to the lipophilic part of the phospholipid bilayer, and the hydrophilic part represented by small orange part aligns itself towards the hydrophilic region of the phospholipid bilayer. b Carpet model of AMPs induced cell killing. Electrostatic bonding between the negatively charged bacterial cell surface and polypeptides aligns parallel to the cell membrane. c Toroidal pore model. AMPs induce the bending of the lipid monolayer in such a way that the polar head groups are both associated with the inserted peptides as well as the lipophilic

Fig. 3

Formulation strategies of Antimicrobial peptides (Martin-Serrano et al. 2019)