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245	1	0	_aCombating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers
490	0		_vNature MicroBiology, 1(Article number 16162), 2016
520	3		_aWith 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.
650	1	4	_aBACTERIA
650	1	4	_aANTIMICROBIAL PEPTIDE POLYMERS
700	1	2	_aLam, S.J.
700	1	2	_aO'Brien-Simpson, N.M.
700	1	2	_aPantarat, N.
700	1	2	_aSulistio, A.
700	1	2	_aWong, E.H.H.
700	1	2	_aChen, Y.-Y.
700	1	2	_aLenzo, J.C.
700	1	2	_aLenzo, J.C.
700	1	2	_aBlencowe, A.
700	1	2	_aReynolds, E.C.
700	1	2	_aQiao, G.G.
856	4	0	_uhttps://drive.google.com/file/d/1yvG5C_SzdnqwTwKdTGcAbx6sBDZPn4nb/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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