lysin
Experimental TherapeuticsDeimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactam AntibioticsThere is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard-of-care (SOC) chemotherapies.
Experimental TherapeuticsSynergistic Activity of Exebacase (CF-301) in Addition to Daptomycin against Staphylococcus aureus in a Neutropenic Murine Thigh Infection ModelWe 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.
Experimental TherapeuticsLinker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal ActivityStreptococcus 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)...
Experimental TherapeuticsExebacase Demonstrates In Vitro Synergy with a Broad Range of Antibiotics against both Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureusIn 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...
Experimental TherapeuticsAntimicrobial Activity of Exebacase (Lysin CF-301) against the Most Common Causes of Infective EndocarditisExebacase, 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...
Editor's Pick Experimental TherapeuticsLysocins: Bioengineered Antimicrobials That Deliver Lysins across the Outer Membrane of Gram-Negative BacteriaThe 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.
Experimental TherapeuticsPostantibiotic and Sub-MIC Effects of Exebacase (Lysin CF-301) Enhance Antimicrobial Activity against Staphylococcus aureusCF-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-...
Experimental TherapeuticsClyJ 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.
Experimental TherapeuticsThe Antistaphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood To Potentiate Methicillin-Resistant Staphylococcus aureus BacteriolysisBacteriophage-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...
Experimental TherapeuticsLysostaphin Lysibody Leads to Effective Opsonization and Killing of Methicillin-Resistant Staphylococcus aureus in a Murine ModelThe 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.