title: Phage endolysins with broad antimicrobial activity against Enterococcus faecalis clinical strains.
abstract: Increasing antibiotic resistance of bacterial pathogens has drawn the attention to the potential use of bacteriophage endolysins as alternative antibacterial agents. Here we have identified, characterized, and studied the lytic potential of two endolysins, Lys168 and Lys170, from phages infecting Enterococcus faecalis. Lys168 and Lys170 belong to the cysteine, histidine-dependent amidohydrolases/peptidases (CHAP) and amidase-2 protein families, respectively. Lys168 is quite a unique enterococcal phage endolysin. It shares 95% amino acidic identity with the endolysin of Staphylococcus aureus phage SAP6, which in turn is distantly related to all known CHAP endolysins of S. aureus phages. Lys170 seems to be a natural chimera assembling catalytic and cell-wall-binding domains of different origin. Both endolysins showed a clear preference to act against E. faecalis and they were able to lyse a high proportion of clinical isolates of this species. Specifically, Lys168 and Lys170 lysed more than 70% and 90% of the tested isolates, respectively, which included a panel of diverse and typed strains representative of highly prevalent clonal complexes. Lys170 was active against all tested E. faecalis VRE strains. The quasi specificity toward E. faecalis is discussed considering the nature of the enzymes' functional domains and the structure of the cell wall peptidoglycan.
authors.affiliation: Technophage, SA, Lisboa, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Proença
authors.forename: Sofia
authors.initials: S
authors.lastname: Fernandes
authors.forename: Clara
authors.initials: C
authors.lastname: Leandro
authors.forename: Filipa Antunes
authors.initials: FA
authors.lastname: Silva
authors.forename: Sofia
authors.initials: S
authors.lastname: Santos
authors.forename: Fátima
authors.initials: F
authors.lastname: Lopes
authors.forename: Rosario
authors.initials: R
authors.lastname: Mato
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 / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D001435:Bacteriophages / Q000737:chemistry*; D002473:Cell Wall / Q000737:chemistry; D003001:Cloning, Molecular; D013293:Enterococcus faecalis / Q000737:chemistry / Q000187:drug effects* / Q000821:virology; D058507:Host Specificity; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D013204:Staphylococcus Phages / Q000737:chemistry; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D011994:Recombinant Proteins; D014764:Viral Proteins; D000581:Amidohydrolases