Therapeutic bacteriophage compositions for treating
The present disclosure relates to a bacteriophage composition comprising one or more (suitably two or more, or three) obligately lytic bacteriophages capable of infecting and lysing Staphylococcus aureus , and use of the same for treating Staphylococcus aureus bacterial infections.
1. A bacteriophage composition substantially free of bacterial components comprising two or more obligately lytic bacteriophages, wherein at least one of the bacteriophages comprises a nucleotide sequence having at least 90% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
2. The bacteriophage composition of claim 1 , wherein the composition's target bacteria range is broader than the range of any individual bacteriophage in the composition.
3. The bacteriophage composition of claim 1 , where the composition comprises at least one bacteriophage comprising a nucleotide sequence having at least 90% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; and at least one additional bacteriophage.
4. The composition of claim 1 , wherein the composition is substantially free of bacterial endotoxin.
5. The composition of claim 1 , wherein the bacterial composition is substantially free of bacterial host protein.
6. The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier, or combinations thereof.
7. The composition of claim 6 , wherein the pharmaceutically acceptable carrier, diluent, excipient or combinations thereof comprises calcium salt or magnesium salt.
8. The composition of claim 1 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.
9. The composition of claim 1 , wherein the two or more bacteriophages infect and lyse methicillin-resistant Staphylococcus aureus or methicillin-sensitive Staphylococcus aureus.
10. The composition of claim 1 , wherein the composition comprises between 1×10 5 and 1×10 11 PFU of each bacteriophage.
11. The composition of claim 1 , wherein the composition is to be administered at a dosage of 1×10 9 to 3×10 11 total PFU per milliliter.
12. The composition of claim 1 , wherein the composition is stored at 2-8° C. or at room temperature.
13. The composition of claim 1 , wherein the nucleotide sequence of at least one bacteriophage in the composition is not naturally-occurring.
14. The composition of claim 1 , wherein the composition comprises two or more bacteriophages, wherein the two or more bacteriophages individually comprise a nucleotide sequence having at least 90% identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
15. The composition of claim 1 , wherein the obligately lytic bacteriophages are capable of complementation.
16. A bacteriophage composition substantially free of bacterial components comprising one or more obligately lytic bacteriophages and a storage medium for storage at a temperature at or below 8° C., wherein the bacteriophage comprises a nucleotide sequence having at least 90% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, wherein each individual bacteriophage is not prone to generalized transduction and does not carry an antibiotic resistance gene.
17. The bacteriophage composition of claim 16 , wherein the storage medium comprises a cryoprotectant.
18. The bacteriophage composition of claim 17 , wherein the cryoprotectant comprises glycerol or sucrose.
19. The bacteriophage composition of claim 18 , wherein the glycerol is in a concentration of about 5% to about 30% (v/v) and the sucrose is in a concentration of about 10% (v/v).
20. The bacteriophage composition of claim 16 , wherein the composition is substantially free of bacterial endotoxin.
21. The composition of claim 16 , wherein the composition is substantially free of bacterial host protein.
22. The composition of claim 16 , wherein the composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier, or combinations thereof.
23. The composition of claim 22 , wherein the pharmaceutically acceptable carrier, diluent, excipient or combinations thereof comprises calcium salt or magnesium salt.
24. The composition of claim 16 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.
25. The composition of claim 16 , wherein the bacteriophages of the composition infect and lyse methicillin-resistant Staphylococcus aureus or methicillin-sensitive Staphylococcus aureus.
26. The composition of claim 16 , wherein the composition comprises between 1×10 5 and 1×10 11 PFU of each bacteriophage.
27. The composition of claim 16 , wherein the composition is to be administered at a dosage ranging between 1×10 9 PFU and 3×10 11 total PFU per milliliter.
28. The composition of claim 16 , wherein the composition is stored at 2-8° C. or at room temperature.
29. The composition of claim 16 , wherein the nucleotide sequence of at least one bacteriophage is not naturally-occurring.
30. The bacteriophage composition of claim 16 , wherein the bacteriophage comprises a nucleotide sequence having at least 93% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
31. A bacteriophage composition substantially free of bacterial components comprising one or more obligately lytic bacteriophages, wherein the bacteriophage comprises a nucleotide sequence having at least 90% but not 100% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, wherein each individual bacteriophage is not prone to generalized transduction and does not carry an antibiotic resistance gene.
32. The bacteriophage composition of claim 31 , wherein the bacteriophage comprises a nucleotide sequence having at least 93% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
33. A bacteriophage composition substantially free of bacterial components comprising one or more non-naturally occurring, obligately lytic bacteriophages, wherein at least one of the bacteriophages comprises a nucleotide sequence having at least 90% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; wherein each individual bacteriophage is not prone to generalized transduction and does not carry an antibiotic resistance gene.
34. The composition of claim 33 , wherein the obligately lytic bacteriophages are capable of complementation.