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US-20260124259-A1 - STAPHYLOCOCCUS PHAGE COMPOSITIONS AND COCKTAILS THEREOF

US20260124259A1US 20260124259 A1US20260124259 A1US 20260124259A1US-20260124259-A1

Abstract

Disclosed here are phage compositions for infecting and/or killing Staphylococcus spp.

Inventors

  • David G. Ousterout
  • Hannah Hewitt TUSON
  • Lana McMILLAN
  • Robert McKee

Assignees

  • Locus Biosciences, Inc.

Dates

Publication Date
20260507
Application Date
20231016

Claims (20)

  1. 1 . A composition comprising at least two bacteriophage, wherein a first bacteriophage is at least 80% identical to p1378 or p4815, and a second bacteriophage is at least 80% identical to p1494e002 or p2808.
  2. 2 . The composition of claim 1 , wherein the first bacteriophage is at least 80% identical to p1378, and the second bacteriophage is at least 80% identical to p1494e002.
  3. 3 . The composition of claim 1 , wherein the first bacteriophage is at least 80% identical to p1378, and the second bacteriophage is at least 80% identical to p2808.
  4. 4 . The composition of claim 1 , wherein the first bacteriophage is at least 80% identical to p4815, and the second bacteriophage is at least 80% identical to p1494e002.
  5. 5 . The composition of claim 1 , wherein the first bacteriophage is at least 80% identical to p4815, and the second bacteriophage is at least 80% identical to p2808.
  6. 6 . The composition of claim 2 , comprising a third bacteriophage at least 80% identical to the p4815.
  7. 7 . The composition of claim 6 , comprising a fourth bacteriophage at least 80% identical to the p2808.
  8. 8 . The composition of claim 3 , comprising a third bacteriophage at least 80% identical to the p4815.
  9. 9 . The composition of claim 4 , comprising a third bacteriophage at least 80% identical to the p2808.
  10. 10 . A composition comprising a plurality of bacteriophage comprising a first bacteriophage and a second bacteriophage, wherein a bacteria treated with the plurality of bacteriophage has a reduced amount of regrowth as compared to treatment with the first bacteriophage or the second bacteriophage alone, wherein the first bacteriophage comprises a Rosenblumvirus and the second bacteriophage comprises a Phietavirus or a Kayvirus.
  11. 11 . The composition of claim 1 , wherein the amount of regrowth is measured by optical density (OD) at a wavelength of 600 nm.
  12. 12 . The composition of claim 10 or claim 11 , wherein the amount of regrowth of the bacteria treated with the plurality of bacteriophage 12 hours after treatment is less than or equal to about 50%, 40%, 30%, 20%, or 10% of regrowth of the bacteria treated with the first bacteriophage.
  13. 13 . The composition of claim 10 or claim 11 , wherein the amount of regrowth of the bacteria treated with the plurality of bacteriophage 12 hours after treatment is less than or equal to about 50%, 40%, 30%, 20%, or 10% of regrowth of the bacteria treated with the second bacteriophage.
  14. 14 . The composition of any one of claims 10-13 , wherein the bacteria is a Staphylococcus bacteria.
  15. 15 . The composition of claim 14 , wherein the bacteria comprise Staphylococcus aureus , methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus salivarius, Staphylococcus argenteus, Staphylococcus hemolyticus , or Staphylococcus schweitzeri, or any combination of two or more thereof.
  16. 16 . The composition of claim 15 , wherein the bacteria comprise the Staphylococcus aureus.
  17. 17 . A bacteriophage engineered to render the bacteriophage lytic by removal, replacement, or inactivation of a lysogenic sequence, wherein the lysogenic sequence comprises at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of a sequence selected from SEQ ID NOS: 49-58.
  18. 18 . The bacteriophage of claim 17 , wherein the bacteriophage is an engineered Phietavirus.
  19. 19 . A composition comprising the bacteriophage of claim 17 or 18 , further comprising a Rosenblumvirus and/or a Kayvirus.
  20. 20 . A method of treating a disease or condition related to Staphylococcus , the method comprising administering to a subject in need thereof the bacteriophage of any one of claims 1-9, 17-18 , or the composition of any one of claim 10-13 or 19 .

Description

CROSS-REFERENCE This application claims the benefit of U.S. Provisional Application No. 63/379,807, filed on Oct. 17, 2022, which is incorporated herein by reference in its entirety. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 53240-754601_SL.xml, created Sep. 21, 2023, which is 4,258,034 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety. SUMMARY In certain aspects, described herein is a composition comprising at least two bacteriophage, wherein a first bacteriophage is at least 80% identical to p1378 or p4815, and a second bacteriophage is at least 80% identical to p1494e002 or p2808. In some embodiments, the first bacteriophage is at least 80% identical to p1378, and the second bacteriophage is at least 80% identical to p1494e002. In some embodiments, the first bacteriophage is at least 80% identical to p1378, and the second bacteriophage is at least 80% identical to p2808. In some embodiments, the first bacteriophage is at least 80% identical to p4815, and the second bacteriophage is at least 80% identical to p1494e002. In some embodiments, the first bacteriophage is at least 80% identical to p4815, and the second bacteriophage is at least 80% identical to p2808. In some embodiments, the composition further comprises comprising a third bacteriophage at least 80% identical to the p4815. In some embodiments, the composition further comprises a fourth bacteriophage at least 80% identical to the p2808. In some embodiments, the composition further comprises a third bacteriophage at least 80% identical to the p4815. In some embodiments, the composition further comprises a third bacteriophage at least 80% identical to the p2808. In certain aspects, described herein is a composition comprising a plurality of bacteriophage comprising a first bacteriophage and a second bacteriophage, wherein a bacteria treated with the plurality of bacteriophage has a reduced amount of regrowth as compared to treatment with the first bacteriophage or the second bacteriophage alone, wherein the first bacteriophage comprises a Rosenblumvirus and the second bacteriophage comprises a Phietavirus or a Kayvirus. In some embodiments, the amount of regrowth is measured by optical density (OD) at a wavelength of 600 nm. In some embodiments, the amount of regrowth of the bacteria treated with the plurality of bacteriophage 12 hours after treatment is less than or equal to about 50%, 40%, 30%, 20%, or 10% of regrowth of the bacteria treated with the first bacteriophage. In some embodiments, the amount of regrowth of the bacteria treated with the plurality of bacteriophage 12 hours after treatment is less than or equal to about 50%, 40%, 30%, 20%, or 10% of regrowth of the bacteria treated with the second bacteriophage. In some embodiments, the bacteria is a Staphylococcus bacteria. In some embodiments, the bacteria comprises Staphylococcus aureus, methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus salivarius, Staphylococcus argenteus, Staphylococcus hemolyticus, or Staphylococcus schweitzeri, or any combination of two or more thereof. In some embodiments, the bacteria comprises the Staphylococcus aureus. In certain aspects, described herein is a bacteriophage engineered to render the bacteriophage lytic by removal, replacement, or inactivation of a lysogenic sequence, wherein the lysogenic sequence comprises at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of a sequence selected from SEQ ID NOS: 49-58. In some embodiments, the bacteriophage is an engineered Phictavirus. In some embodiments, described herein is a composition comprising the bacteriophage described herein, further comprising a Rosenblumvirus and/or a Kayvirus. In some embodiments, described herein is a method of treating a disease or condition related to Staphylococcus, the method comprising administering to a subject in need thereof the bacteriophage described herein, or the composition described herein. In some embodiments, Staphylococcus is causative of, and/or contributes to, the disease or condition. In certain aspects, described herein is a bacteriophage comprising at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with p1378 (PTA-127329). In certain aspects, described herein is a bacteriophage comprising at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with p4815 (PTA-127331). In certain aspects, described herein is a bacteriophage comprising at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with p1494e002 (PTA-127345). In certain aspects, described herein is a bacteriophage comprising at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with p2808 (PTA-127332). In certain aspects, described herein is a composition comprising at least two bacterioph