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Antimicrob Agents Chemother. 2014 Jul;58(7):3774-84. doi: 10.1128/AAC.02668-14. Epub 2014 Apr 21.

Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa.

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Laboratory of Gene Technology, Department Biosystems, KU Leuven, Heverlee, Belgium.
Lisando GmbH, Regensburg, Germany.
Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium.
Centre of Microbial and Plant Genetics, Department Microbial and Molecular Systems, KU Leuven, Heverlee, Belgium.
Laboratory of Food Microbiology, Department of Microbial and Molecular Systems, KU Leuven, Heverlee, Belgium.
Laboratory of Gene Technology, Department Biosystems, KU Leuven, Heverlee, Belgium


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 transports 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 composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the 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 units) manner. Time-lapse microscopy confirms that Art-175 punctures the peptidoglycan layer within 1 min, 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 >4 log units compared to that of the untreated controls). In summary, Art-175 is a novel antibacterial that is well suited for a broad range of applications in hygiene and veterinary and human medicine, with a unique potential to target persister-driven chronic infections.

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