Lam, S.J. O'Brien-Simpson, N.M. Pantarat, N. Sulistio, A. Wong, E.H.H. Chen, Y.-Y. Lenzo, J.C. Lenzo, J.C. Blencowe, A. Reynolds, E.C. Qiao, G.G. text xx 9999 monographic und

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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. BACTERIA ANTIMICROBIAL PEPTIDE POLYMERS https://drive.google.com/file/d/1yvG5C_SzdnqwTwKdTGcAbx6sBDZPn4nb/view?usp=drivesdk https://drive.google.com/file/d/1yvG5C_SzdnqwTwKdTGcAbx6sBDZPn4nb/view?usp=drivesdk 250602 20260521091519.0