US2022064615A1PendingUtilityA1

Streptococcus bacteriophage lysins for detection and treatment of gram positive bacteria

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Assignee: UNIV ROCKEFELLERPriority: Apr 21, 2011Filed: Sep 15, 2021Published: Mar 3, 2022
Est. expiryApr 21, 2031(~4.7 yrs left)· nominal 20-yr term from priority
Inventors:Vincent FischettiJonathan SchmitzDaniel GilmerChad Euler
C12Y 302/01017A61K 38/162A61P 31/04C12N 9/2462A61K 38/50C12N 9/78A61K 45/06A61K 38/47A61K 38/00A61P 43/00
76
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Claims

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.

Claims

exact text as granted — not AI-modified
1 - 42 . (canceled) 
     
     
         43 . 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 catalytic 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 catalytic domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to kill  Staphylococcus  and  Streptococcus  bacteria, in an amount effective to kill the  Staphylococcus  and  Streptococcus  bacteria. 
     
     
         44 . The method of  claim 43 , wherein the catalytic domain comprises SEQ ID NO:4 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:4 and biologically active to kill  Staphylococcus  and  Streptococcus  bacteria. 
     
     
         45 . The method of  claim 43 , wherein the bacteria is an antibiotic resistant bacteria. 
     
     
         46 . The method of  claim 43 , wherein the bacteria is methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin intermediate-sensitivity  Staphylococcus aureus  (VISA), or vancomycin resistant  Staphylococcus aureus  (VRSA). 
     
     
         47 . The method of  claim 43 , wherein the chimeric protein is provided as a pharmaceutical composition comprising the chimeric protein combined with other components selected from one or more of a carrier, vehicle, polypeptide, polynucleotide, holin protein(s), one or more antibiotics or suitable excipients. 
     
     
         48 . The method of  claim 43 , wherein the chimeric protein is a chimeric lytic enzyme comprising the catalytic 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, wherein said catalytic domain is operably linked to a binding domain of another lysin. 
     
     
         49 . The method of  claim 48 , wherein the bacteria is an antibiotic resistant bacteria. 
     
     
         50 . The method of  claim 49 , wherein the bacteria is methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin intermediate-sensitivity  Staphylococcus aureus  (VISA), or vancomycin resistant  Staphylococcus aureus  (VRSA). 
     
     
         51 . 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 catalytic 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 catalytic domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to kill  Staphylococcus  and  Streptococcus  bacteria, in an amount effective to treat the infection. 
     
     
         52 . The method of  claim 51 , wherein the catalytic domain comprises SEQ ID NO:4 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:4 and biologically active to kill  Staphylococcus  and  Streptococcus  bacteria. 
     
     
         53 . The method of  claim 51 , wherein the bacteria is methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin intermediate-sensitivity  Staphylococcus aureus  (VISA), or vancomycin resistant  Staphylococcus aureus  (VRSA). 
     
     
         54 . The method of  claim 51 , wherein the chimeric protein is a chimeric lytic enzyme comprising the catalytic 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, wherein said catalytic domain is operably linked to a binding domain of another lysin. 
     
     
         55 . 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 the chimeric protein of  claim 43 , whereby the number of  Staphylococcus, Streptococcus, Listeria monocytogenes  or  Enterococcus faecalis  bacteria in the human is reduced and the infection is controlled. 
     
     
         56 . The method of  claim 55  wherein the bacteria is selected from  Staphylococcus aureus, Staphylococcus simulans, Streptococcus suis, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae  (GBS),  Streptococcus pyogenes  (GAS),  Streptococcus sanguinis, Streptococcus gordonii, Streptococcus dysgalactiae, Streptococcus  GES, and  Streptococcus pneumonia.    
     
     
         57 . The method of  claim 55 , wherein the catalytic domain comprises SEQ ID NO:4 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:4 and biologically active to kill  Staphylococcus  and  Streptococcus  bacteria. 
     
     
         58 . The method of  claim 55 , wherein the chimeric protein is formulated as a topical or dermatological composition for administration to the skin or external surface of a human. 
     
     
         59 . The method of  claim 55 , further comprising administering one or more antibiotic. 
     
     
         60 . The method of  claim 55 , wherein the chimeric protein is a chimeric lytic enzyme comprising the catalytic 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, wherein said catalytic domain is operably linked to a binding domain of another lysin. 
     
     
         61 . The method of  claim 60  wherein the bacteria is an antibiotic resistant bacteria and is selected from methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin intermediate-sensitivity  Staphylococcus aureus  (VISA), or vancomycin resistant  Staphylococcus aureus  (VRSA). 
     
     
         62 . A method for treating a human subject exposed to or at risk for exposure to gram positive bacteria selected from a  Staphylococcus  strain,  Streptococcus  strain,  Listeria monocytogenes  or  Enterococcus faecalis  bacteria, comprising the step of administering to the human subject a chimeric protein comprising the catalytic 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 the gram positive bacteria, said catalytic domain operably linked or covalently attached to a heterologous protein or polypeptide, wherein the chimeric protein is biologically active to kill the gram positive bacteria selected from a  Staphylococcus  strain,  Streptococcus  strain,  Listeria monocytogenes  or  Enterococcus faecalis  bacteria, in an amount effective to kill the  Staphylococcus  strain,  Streptococcus  strain,  Listeria monocytogenes  or  Enterococcus faecalis  bacteria. 
     
     
         63 . The method of  claim 62 , wherein the subject is exposed to or at risk of  Staphylococcus aureus,  Group B  Streptococcus  bacteria (GBS),  Streptococcus pyogenes  (GAS) or  Streptococcus pneumonia.    
     
     
         64 . The method of  claim 62 , wherein the catalytic domain comprises SEQ ID NO:4 or variants thereof having at least 80% identity to the polypeptide of SEQ ID NO:4 and biologically active to kill  Staphylococcus  and  Streptococcus  bacteria. 
     
     
         65 . The method of  claim 62 , further comprising administering one or more antibiotic. 
     
     
         66 . The method of  claim 62 , wherein the chimeric protein is a chimeric lytic enzyme comprising the catalytic 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 the gram positive bacteria selected from a  Staphylococcus  strain,  Streptococcus  strain,  Listeria monocytogenes  or  Enterococcus faecalis  bacteria, wherein said catalytic domain is operably linked to a binding domain of another lysin. 
     
     
         67 . The method of  claim 62 , wherein the bacteria is an antibiotic resistant bacteria and is selected from methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin intermediate-sensitivity  Staphylococcus aureus  (VISA), or vancomycin resistant  Staphylococcus aureus  (VRSA).

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