title: Novel chimerical endolysins with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus.
abstract: Due to their bacterial lytic action, bacteriophage endolysins have recently gained great attention as a potential alternative to antibiotics in the combat of Gram-positive pathogenic bacteria, particularly those displaying multidrug resistance. However, large-scale production and purification of endolysins is frequently impaired due to their low solubility. In addition, a large number of endolysins appear to exhibit reduced lytic efficacy when compared with their action during phage infection. Here, we took advantage of the high solubility of two recently characterized enterococcal endolysins to construct chimeras targeting Staphylococcus aureus. The putative cell wall binding domain of these endolysins was substituted by that of a staphylococcal endolysin that showed poor solubility. Under appropriate conditions the resulting chimeras presented the high solubility of the parental enterococcal endolysins. In addition, they proved to be broadly active against a collection of the most relevant methicillin-resistant S. aureus epidemic clones and against other Gram-positive pathogens. Thus, fusion of endolysin domains of heterologous origin seems to be a suitable approach to design new potent endolysins with changed and/or extended lytic spectrum that are amenable to large-scale production.
authors.affiliation: Technophage, SA, Lisboa, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Fernandes
authors.forename: Daniela
authors.initials: D
authors.lastname: Proença
authors.forename: Cátia
authors.initials: C
authors.lastname: Cantante
authors.forename: Filipa Antunes
authors.initials: FA
authors.lastname: Silva
authors.forename: Clara
authors.initials: C
authors.lastname: Leandro
authors.forename: Sara
authors.initials: S
authors.lastname: Lourenço
authors.forename: Catarina
authors.initials: C
authors.lastname: Milheiriço
authors.forename: Hermínia
authors.initials: H
authors.lastname: de Lencastre
authors.forename: Patrícia
authors.initials: P
authors.lastname: Cavaco-Silva
authors.forename: Madalena
authors.initials: M
authors.lastname: Pimentel
authors.forename: Carlos
authors.initials: C
authors.lastname: São-José
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry; D003001:Cloning, Molecular; D013293:Enterococcus faecalis / Q000737:chemistry / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D010457:Peptidoglycan / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012995:Solubility; D013204:Staphylococcus Phages / Q000737:chemistry; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D000581:Amidohydrolases