Streptococcus bacteriophage lysins for detection and treatment of gram positive bacteria
AssigneeThe Rockefeller University
InventorsVincent A. Fischetti, Jonathan Schmitz, Daniel Gilmer, Chad Euler
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Abstract
The present invention provides methods, compositions and articles of manufacture useful for the prophylactic and therapeutic amelioration and treatment of gram-positive bacteria, including Streptococcus and Staphylococcus, and related conditions. The invention provides compositions and methods incorporating and utilizing Streptococcus suis derived bacteriophage lysins, particularly PlySs2 and/or PlySs1 lytic enzymes and variants thereof, including truncations thereof. Methods for treatment of humans are provided.
Claims23
A method for killing Staphylococcus and Streptococcus bacteria or for reducing a population of Staphylococcus and Streptococcus bacteria comprising the step of contacting the bacteria with a chimeric protein comprising the binding domain of the isolated lysin polypeptide comprising the amino acid sequence of SEQ ID NO:3 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:3 and effective to kill Staphylococcus and Streptococcus bacteria, said binding domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to bind Staphylococcus and Streptococcus bacteria and kill the Staphylococcus and Streptococcus bacteria.
A method for treating an antibiotic-resistant Staphylococcus aureus infection in a human, comprising the step of administering to the human a chimeric protein comprising the binding domain of the isolated lysin polypeptide comprising the amino acid sequence of SEQ ID NO:3 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:3 and effective to kill Staphylococcus and Streptococcus bacteria, said binding domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to bind Staphylococcus and Streptococcus bacteria and effective to treat the Staphylococcus aureus infection.
A method for treating gram-positive bacterial infection or for reducing or controlling gram-positive bacterial infection or contamination caused by Staphylococcus strains, Streptococcus strains, Listeria monocytogenes or Enterococcus faecalis bacteria in a human, comprising the step of administering to the human an effective amount of a chimeric protein comprising the binding domain of the isolated lysin polypeptide comprising the amino acid sequence of SEQ ID NO:3 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:3 and effective to kill Staphylococcus and Streptococcus bacteria, said binding domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to bind Staphylococcus and Streptococcus bacteria, whereby the number of Staphylococcus, Streptococcus, Listeria monocytogenes or Enterococcus faecalis bacteria in the human is reduced and the infection is controlled.
A method for treating a human subject exposed to or at risk for exposure to a pathogenic Staphylococcus strain, Streptococcus strain, Listeria monocytogenes or Enterococcus faecalis bacteria, comprising the step of administering to the human subject a chimeric protein comprising the binding domain of the isolated lysin polypeptide comprising the amino acid sequence of SEQ ID NO:3 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:3 and effective to kill Staphylococcus and Streptococcus bacteria, said binding domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to bind Staphylococcus and Streptococcus bacteria and kill the Staphylococcus, Streptococcus, Listeria monocytogenes or Enterococcus faecalis bacteria.
Dependencies are inferred from the claim text.