02572nam a2200325Ia 4500003001000000005001700010040000900027090001200036245012100048490005500169520145300224650001301677650003501690700001401725700002601739700001701765700001701782700001701799700001601816700001601832700001601848700001701864700001901881700001501900856015601915942001402071008004102085999001702126952010302143MX-MdCICY20260521091519.0  cCICY  aB-1625510aCombating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers0 vNature MicroBiology, 1(Article number 16162), 20163 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.14aBACTERIA14aANTIMICROBIAL PEPTIDE POLYMERS12aLam, S.J.12aO'Brien-Simpson, N.M.12aPantarat, N.12aSulistio, A.12aWong, E.H.H.12aChen, Y.-Y.12aLenzo, J.C.12aLenzo, J.C.12aBlencowe, A.12aReynolds, E.C.12aQiao, G.G.40uhttps://drive.google.com/file/d/1yvG5C_SzdnqwTwKdTGcAbx6sBDZPn4nb/view?usp=drivesdkzPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx  2LoccREF1250602s9999    xx |||||s2   |||| ||und|d  c26368d26368  00102Loc40708F1aCICYbCICYcREd2025-06-25l0oB-16255r2025-06-25 16:01:48w2025-06-25yREF1