title: Breaking barriers: expansion of the use of endolysins as novel antibacterials against Gram-negative bacteria.
abstract: The emergence and spread of antibiotic-resistant bacteria drives the search for novel classes of antibiotics to replenish our armamentarium against bacterial infections. This is particularly critical for Gram-negative pathogens, which are intrinsically resistant to many existing classes of antibiotics due to the presence of a protective outer membrane. In addition, the antibiotics development pipeline is mainly oriented to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus. A promising novel class of antibacterials is endolysins. These enzymes encoded by bacterial viruses hydrolyze the peptidoglycan layer with high efficiency, resulting in abrupt osmotic lysis and cell death. Their potential as novel antibacterials to treat Gram-positive bacteria has been extensively demonstrated; however, the Gram-negative outer membrane has presented a formidable barrier for the use of endolysins against Gram-negatives until recently. This review reports on the most recent advances in the development of endolysins to kill Gram-negative species with a special focus on endolysin-engineered Artilysins(®).
authors: Laboratory of Gene Technology, Department Biosystems, University of Leuven, Kasteelpark Arenberg 21, box 2462, B-3001 Leuven, Belgium.
authors: Yves
authors: Y
authors: Briers
authors: Rob
authors: R
authors: Lavigne
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D001433:Bacteriolysis; D010450:Endopeptidases / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000662:veterinary; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D010457:Peptidoglycan / Q000378:metabolism; D015202:Protein Engineering
chemical_list: D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D010450:Endopeptidases; C001143:endolysin
keywords: Art-175; Artilysin®; Gram-negative; antibiotic resistance; endolysin; novel antibiotics; outer membrane