TY  - BOOK
AU  - Lam,S.J.
AU  - O'Brien-Simpson,N.M.
AU  - Pantarat,N.
AU  - Sulistio,A.
AU  - Wong,E.H.H.
AU  - Chen,Y.-Y.
AU  - Lenzo,J.C.
AU  - Lenzo,J.C.
AU  - Blencowe,A.
AU  - Reynolds,E.C.
AU  - Qiao,G.G.
TI  - Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers
KW  - BACTERIA
KW  - ANTIMICROBIAL PEPTIDE POLYMERS
N2  - 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
UR  - https://drive.google.com/file/d/1yvG5C_SzdnqwTwKdTGcAbx6sBDZPn4nb/view?usp=drivesdk
ER  -