Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers
Date
2016
Authors
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.
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Journal article
Citation
Nature Microbiology, 2016; 1(11, article no. 16162):1-11
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Abstract
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-μM 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.
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Data source: Supplementary information, http://www.nature.com/articles/nmicrobiol2016162#supplementary-information
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Copyright 2016 Macmillan Publishers