Bacteriophage lysin and antibiotic combinations against gram positive bacteria

Abstract

The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

1 - 27 . (canceled) 
     
     
         28 . A method of treating a  Staphylococcus  bacterial infection in a subject comprising administering to the subject a combination comprising bacteriophage lysin PlySs2 and antibiotic daptomycin, wherein the PlySs2 lysin comprises the amino acid sequence set out in SEQ ID NO: 1 or variants thereof having at least 90% amino acid identity to SEQ ID NO: 1 and effective to kill the  Staphylococcus  bacteria, and wherein the combination is effective to reduce the minimally-inhibitory concentration (MIC) dose for daptomycin and PlySs2 lysin and wherein the combination renders daptomycin effective in the presence of pulmonary surfactant and for treatment of pneumonia. 
     
     
         29 . The method of  claim 28  wherein the bacterial infection is a  S. aureus  infection. 
     
     
         30 . The method of  claim 28  wherein the infection is due to an antibiotic-resistant Staphylococcal bacteria. 
     
     
         31 . The method of  claim 30  wherein the bacteria is methicillin-resistant  S. aureus  (MRSA). 
     
     
         32 . The method of  claim 30  wherein the bacteria is vancomycin-resistant  S. aureus  (VRSA). 
     
     
         33 . The method of  claim 28  wherein the subject has skin and soft tissue infection, bacteremia, endocarditis or pneumonia. 
     
     
         34 . The method of  claim 28  wherein both the daptomycin and the PlySs2 lysin are effective in the combination at doses below their MIC dose. 
     
     
         35 . A method of treating a  Streptococcus  bacterial infection in a subject comprising administering to the subject a combination comprising bacteriophage lysin PlySs2 and antibiotic daptomycin, wherein the PlySs2 lysin comprises the amino acid sequence set out in SEQ ID NO: 1 or variants thereof having at least 90% amino acid identity to SEQ ID NO: 1 and effective to kill the  Streptococcus  bacteria, and wherein the combination is effective to reduce the minimally-inhibitory concentration (MIC) dose for daptomycin and PlySs2 lysin and wherein the combination renders daptomycin effective in the presence of pulmonary surfactant and for treatment of pneumonia. 
     
     
         36 . The method of  claim 35  wherein the bacterial infection is a  Streptococcus pneumonia  infection. 
     
     
         37 . The method of  claim 35  wherein the bacterial infection is a Group A or Group B Streptococcal infection. 
     
     
         38 . The method of  claim 35  wherein the infection is due to an antibiotic-resistant Streptococcal bacteria. 
     
     
         39 . The method of  claim 35  wherein both the daptomycin and the PlySs2 lysin are effective in the combination at doses below their MIC dose. 
     
     
         40 . A method of reducing the development of antibiotic-resistant  Staphylococcus  bacteria in a subject upon administration of daptomycin by administering a combination comprising bacteriophage lysin PlySs2 and antibiotic daptomycin, wherein the PlySs2 lysin comprises the amino acid sequence set out in SEQ ID NO:1 or variants thereof having at least 90% amino acid identity to SEQ ID NO: 1 and effective to kill the  Staphylococcus  bacteria, and wherein the combination is effective to reduce the development of antibiotic-resistant gram positive bacteria and the minimally-inhibitory concentration (MIC) dose for daptomycin and PlySs2 lysin and wherein the combination renders daptomycin effective in the presence of pulmonary surfactant and for treatment of pneumonia, whereby antibiotic resistance is suppressed relative to administration of daptomycin alone. 
     
     
         41 . The method of  claim 40  wherein both the daptomycin and the PlySs2 lysin are effective in the combination at doses below their MIC dose. 
     
     
         42 . The method of  claim 40  wherein antibiotic-resistant bacteria have increased sensitivity to PlySs2 lysin compared to antibiotic sensitive gram-positive bacteria.