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lysin

  • Synergistic Activity of Exebacase (CF-301) in Addition to Daptomycin against <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> in a Neutropenic Murine Thigh Infection Model
    Experimental Therapeutics
    Synergistic Activity of Exebacase (CF-301) in Addition to Daptomycin against Staphylococcus aureus in a Neutropenic Murine Thigh Infection Model

    We evaluated the efficacy of escalating doses of exebacase administered with subtherapeutic daptomycin exposures against 8 Staphylococcus aureus isolates in a neutropenic murine thigh infection model. Daptomycin alone resulted in mean growth of 0.39 ± 1.19 log10 CFU/thigh.

    Tomefa E. Asempa, Kamilia Abdelraouf, Teresa Carabeo, Raymond Schuch, David P. Nicolau
  • Linker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal Activity
    Experimental Therapeutics
    Linker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal Activity

    Streptococcus pneumoniae is a leading human pathogen uniquely characterized by choline moieties on the bacterial surface. Our previous work reported a pneumococcus-specific chimeric lysin, ClyJ, which combines the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) enzymatically active domain (EAD) from the PlyC lysin and the cell wall binding domain (CBD)...

    Hang Yang, Dehua Luo, Irina Etobayeva, Xiaohong Li, Yujing Gong, Shujuan Wang, Qiong Li, Poshi Xu, Wen Yin, Jin He, Daniel C. Nelson, Hongping Wei
  • Exebacase Demonstrates <em>In Vitro</em> Synergy with a Broad Range of Antibiotics against both Methicillin-Resistant and Methicillin-Susceptible <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span>
    Experimental Therapeutics
    Exebacase Demonstrates In Vitro Synergy with a Broad Range of Antibiotics against both Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus

    In vitro synergy between an antimicrobial protein lysin (cell wall hydrolase) called exebacase and each of 12 different antibiotics was examined against Staphylococcus aureus isolates using a nonstandard medium approved for exebacase susceptibility testing by the Clinical and Laboratory Standards Institute. In the checkerboard assay format, fractional...

    Aubrey Watson, Karen Sauve, Cara Cassino, Raymond Schuch
  • Antimicrobial Activity of Exebacase (Lysin CF-301) against the Most Common Causes of Infective Endocarditis
    Experimental Therapeutics
    Antimicrobial Activity of Exebacase (Lysin CF-301) against the Most Common Causes of Infective Endocarditis

    Exebacase, a recombinantly produced lysin (cell wall hydrolase), and comparator antibiotics were tested by the broth microdilution method against strain sets of Staphylococcus and Streptococcus spp., which are the most common causes of infective endocarditis in humans. Exebacase was active against all Staphylococcus spp. tested, including S. aureus...

    Aubrey Watson, Jun Taek Oh, Karen Sauve, Patricia A. Bradford, Cara Cassino, Raymond Schuch
  • Lysocins: Bioengineered Antimicrobials That Deliver Lysins across the Outer Membrane of Gram-Negative Bacteria
    Editor's Pick Experimental Therapeutics
    Lysocins: Bioengineered Antimicrobials That Deliver Lysins across the Outer Membrane of Gram-Negative Bacteria

    The prevalence of multidrug-resistant Pseudomonas aeruginosa has stimulated development of alternative therapeutics. Bacteriophage peptidoglycan hydrolases, termed lysins, represent an emerging antimicrobial option for targeting Gram-positive bacteria.

    Ryan D. Heselpoth, Chad W. Euler, Raymond Schuch, Vincent A. Fischetti
  • Postantibiotic and Sub-MIC Effects of Exebacase (Lysin CF-301) Enhance Antimicrobial Activity against <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span>
    Experimental Therapeutics
    Postantibiotic and Sub-MIC Effects of Exebacase (Lysin CF-301) Enhance Antimicrobial Activity against Staphylococcus aureus

    CF-301 (exebacase) is a recombinantly produced bacteriophage-derived lysin (cell wall hydrolase) and is the first agent of this class to enter clinical development in the United States for treating bacteremia including endocarditis due to Staphylococcus aureus. Whereas rapid bactericidal activity is the hallmark in vitro and in vivo response to CF-...

    Jun Taek Oh, Cara Cassino, Raymond Schuch
  • ClyJ Is a Novel Pneumococcal Chimeric Lysin with a Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase Catalytic Domain
    Experimental Therapeutics
    ClyJ Is a Novel Pneumococcal Chimeric Lysin with a Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase Catalytic Domain

    Streptococcus pneumoniae is one of the leading pathogens that cause a variety of mucosal and invasive infections. With the increased emergence of multidrug-resistant S. pneumoniae, new antimicrobials with mechanisms of action different from conventional antibiotics are urgently needed.

    ...
    Hang Yang, Yujing Gong, Huaidong Zhang, Irina Etobayeva, Paulina Miernikiewicz, Dehua Luo, Xiaohong Li, Xiaoxu Zhang, Krystyna Dąbrowska, Daniel C. Nelson, Jin He, Hongping Wei
  • The Antistaphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood To Potentiate Methicillin-Resistant <em>Staphylococcus aureus</em> Bacteriolysis
    Experimental Therapeutics
    The Antistaphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood To Potentiate Methicillin-Resistant Staphylococcus aureus Bacteriolysis

    Bacteriophage-derived lysins are cell-wall-hydrolytic enzymes that represent a potential new class of antibacterial therapeutics in development to address burgeoning antimicrobial resistance. CF-301, the lead compound in this class, is in clinical development as an adjunctive treatment to potentially improve clinical cure rates of Staphylococcus aureus bacteremia and...

    Chiara Indiani, Karen Sauve, Assaf Raz, Wessam Abdelhady, Yan Q. Xiong, Cara Cassino, Arnold S. Bayer, Raymond Schuch
  • Lysostaphin Lysibody Leads to Effective Opsonization and Killing of Methicillin-Resistant <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> in a Murine Model
    Experimental Therapeutics
    Lysostaphin Lysibody Leads to Effective Opsonization and Killing of Methicillin-Resistant Staphylococcus aureus in a Murine Model

    The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate structures that are highly conserved. While these properties make surface carbohydrates ideal targets for immunotherapy, carbohydrates elicit a poor immune response that results primarily in low-affinity IgM antibodies.

    Assaf Raz, Anna Serrano, Maneesha Thaker, Tricia Alston, Vincent A. Fischetti
  • Experimental Therapeutics
    Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
    Raymond Schuch, Babar K. Khan, Assaf Raz, Jimmy A. Rotolo, Michael Wittekind
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