Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers

Author: Lam, S.J.; O’Brien-Simpson, N.M.; Pantarat, N.; Sulistio, A.; Wong, E.H.H.; Chen, Y.-Y.; Lenzo, J.C.; Holden, J.A.; Blencowe, A.; Reynolds, E.C.; Qiao, G.G.

Description: With the recent emergence of reports on resistant Gram-negative ‘superbugs’, infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed ‘structurally nanoengineered antimicrobial peptide polymers’ (SNAPPs) exhibit sub-muM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy. Furthermore, we did not observe any resistance acquisition by A. baumannii (including the CMDR strain) to SNAPPs. Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway, possibly accounting for why we did not observe resistance to SNAPPs in CMDR bacteria. Overall, SNAPPs show great promise as low-cost and effective antimicrobial agents and may represent a weapon in combating the growing threat of MDR Gram-negative bacteria.

Subject Headings: Acinetobacter Infections/drug therapy/microbiology; Acinetobacter baumannii/drug effects/pathogenicity; Animals; Antimicrobial Cationic Peptides/chemistry/pharmacology/therapeutic use; Drug Resistance, Multiple, Bacterial; Escherichia coli/drug effects/pathogenicity; Gram-Negative Bacteria/drug effects; Gram-Negative Bacterial Infections/drug therapy/microbiology; Mice; Nanoparticles/chemistry; Nanotechnology/economics/methods; Peritonitis/drug therapy/microbiology

Keywords: Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers

Publication year: 2016

Journal or book title: Nature Microbiology

Volume: 1

Issue: 11

Pages: 16162

Find the full text :

Find more like this one (cited by):,16&hl=en

Type: Journal Article

Serial number: 2708