Novel chimerical endolysins with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus
| Autor: | Madalena Pimentel, Rodrigues Leandro Clara Isabel, Ferreira Llorente Grancho Lourenco Sara, Catarina Milheiriço, Filipa Silva, Cátia Cantante, Daniela Proença, Sofia Fernandes, Hermínia de Lencastre, Patrícia Cavaco-Silva, Carlos São-José |
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| Rok vydání: | 2012 |
| Předmět: |
Microbiology (medical)
Methicillin-Resistant Staphylococcus aureus Recombinant Fusion Proteins Immunology Lysin Peptidoglycan medicine.disease_cause Microbiology Amidohydrolases Bacteriophage Structure-Activity Relationship Viral Proteins Cell Wall medicine Enterococcus faecalis Cloning Molecular Escherichia coli Pharmacology biology Pathogenic bacteria biology.organism_classification Antimicrobial Virology Anti-Bacterial Agents Protein Structure Tertiary Multiple drug resistance Lytic cycle Solubility Staphylococcus aureus Staphylococcus Phages |
| Zdroj: | Microbial drug resistance (Larchmont, N.Y.). 18(3) |
| ISSN: | 1931-8448 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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