Phage-associated lytic enzymes for treatment of Streptococcus pneumoniae and related conditions

An article of manufacture comprising a packaging material and a therapeutic composition contained within the packaging material,

• a. the therapeutic composition comprising a Pal lytic enzyme that comprises the amino acid sequence of SEQ ID NO:1 where the Pal lytic enzyme is characterized by one or more of the following functions:
• an In vitro Killing Assay comprising treatment of an exponentially growing population of S. pneumoniae bacteria with 100 enzyme units (U) of the lytic enzyme per mL in an enzyme buffer for about 30 seconds results in a decrease in the viable titer of the S. pneumoniae bacteria by at least 3.3 in a log10 scale of colony forming units/ml, as compared to performing an In vitro Killing Assay using the enzyme buffer, where the enzyme buffer consists essentially of:
• 20 mM phosphate buffer (PB), 1 mM EDTA and 10 mM DTT alone;
• ii. an In vitro Killing Assay comprising treatment of a stationary phase of a population of S. pneumoniae bacteria with 10,000 enzyme units (U)/ml of the lytic enzyme in an enzyme buffer for about 30 seconds results in a decrease in the viable titer of the S. pneumoniae bacteria by at least 3.0 in a log10 scale of colony forming units/ml, as compared to perfoming an In vitro Killing Assay using the enzyme buffer, where the enzyme buffer consists essentially of:
• 20 mM phosphate buffer (PB), 1 mM EDTA and 10 mM DTT alone;
• and
• iii. an In vivo Nasal Infection Assay comprising administering about 108 colony forming units of S. pneumoniae bacteria, followed by administration 42 hours later of about 1400 enzyme units (U) of the lytic enzyme results in a reduction of the S. pneumoniae population to 0 in a log10 scale/10 microliters nasal wash;
• and
• b. the packaging material comprising a label that indicates that the therapeutic composition can be used for treating one or more conditions selected from the group consisting of:
• exposure to S. pneumoniae bacteria, and infection by S. pneumoniae bacteria.

A method for treating a penicillin-resistant Streptococcus pneumoniae infection comprising the step of administering to a subject, having a penicillin-resistant Streptococcus pneumoniae infection, an effective amount of a composition comprising an isolated polypeptide including the amino acid sequence of SEQ ID NO:1 and where the method is further characterized by one or more of the following:

• (a) the isolated polypeptide is a shuffled lytic enzyme, a chimeric lytic enzyme or a combination thereof
• (b) the composition further comprises a holin protein;
• (c) the composition is administered parenterally;
• and
• (d) the method is a method for treating endocarditis, thereby treating the penicillin-resistant infection.