Title: Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa
Authors: Briers, Yves
Walmagh, Maarten
Grymonprez, Barbara
Biebl, Manfred
Pirnay, Jean-Paul
Defraine, Valerie
Michiels, Jan
Cenens, William
Aertsen, Abram
Miller, Stefan
Lavigne, Rob # ×
Issue Date: Jul-2014
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:58 issue:7 pages:3774-3784
Abstract: Artilysins constitute a novel class of efficient enzyme-based antibacterials. Specifically, they covalently combine a bacteriophage-encoded endolysin, which degrades the peptidoglycan, with a targeting peptide that transfers the endolysin through the outer membrane of Gram-negative bacteria. Art-085 as well as Art-175, its optimized homolog with increased thermostability, are each comprised of the 29 amino acid SMAP-29 peptide fused to KZ144 endolysin. In contrast to KZ144, Art-085 and Art-175 pass the outer membrane and kill Pseudomonas aeruginosa, including multidrug-resistant strains, in a rapid and efficient (∼5 log) manner. Time-lapse microscopy confirms that Art-175 punctures the peptidoglycan layer within a minute, inducing a bulging membrane and complete lysis. Art-175 is highly refractory to resistance development by naturally occurring mutations. In addition, the resistance mechanisms against 21 therapeutically used antibiotics do not show cross-resistance to Art-175. Since Art-175 does not require an active metabolism for its activity, it has a superior bactericidal effect against P. aeruginosa persisters (up to more than 4 log). In summary, Art-175 is a novel antibacterial well suited for a broad range of applications in hygiene, veterinary and human medicine, with the unique potential to target persister-driven chronic infections.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Division of Gene Technology (-)
Centre of Microbial and Plant Genetics
Centre for Food and Microbial Technology
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
Briersetal_AAC.pdf Published 1014KbAdobe PDFView/Open


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science