Bacteriophage for modulating inflammatory bowel disease
Disclosed herein are bacteriophage compositions and therapeutic uses thereof. The disclosure also relates to bacteriophage that are capable of lysing Klebsiella bacterial strains, e.g., strains that are associated with inflammatory bowel disease, and thereby capable of modulating disease.
1. A method of treating an inflammatory bowel disease comprising administering to a subject in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable carrier; and lytic bacteriophages selected from at least three of the following groups:
a) Group 1: 1.2-2, colon-11, PKP-55, or a family Myoviridae, subfamily Tevenvirinae, genus Kp15 virus that is capable of infecting at least two of Klebsiella pneumoniae strains: KP2, CT-123-1, MKP2_21611, and MKP2_251_B;
b) Group 2: M16-7a, KP2-4a, M16-4a, colon-36, KP2-5-1, 1.2-4br, 1.2-4s, M16-6c, KP2-9a, M16-9a, KP2-5a, colon-14-15, colon-6, colon1, M16-3-2c, M16-5c, or a family Myoviridae, subfamily Tevenvirinae, genus T4 virus that is capable of infecting at least two of Klebsiella pneumoniae strains: KP2, CT-123-1, MKP2_2161 1, and MKP2_251_B;
c) Group 3: KP2-15-2-1, KP2-14, KP2-15-1, colon-14, 1.2-3b, KP2-8c, KP2-7c, KP2-7-1c, KP2-8a, KP2-5, KP2-16-1, or a Podoviridae, subfamily Autographivirinae, genus T7 virus that is capable of infecting Klebsiella pneumoniae strains KP2 and MKP2_251_B;
d) Group 4: MCoc4c, MCoc6c, Mcoc7c, MCoc3c, MCoc5c, MCoc15c, MCoc8a, MCoc9-2c, M16-9-1c, MCoc9-1c, or Podoviridae, subfamily Autographivirinae, genus Kp34 virus that is capable of infecting at least three of Klebsiella pneumoniae strains: CT-141-1, CT-123-1, MKP2_2161 1, and MKP2_251_C;
e) Group 5: 8M-8, or a family Myoviridae, subfamily Vequintavirinae, genus Sc1 virus that is capable of infecting Klebsiella pneumoniae strains CT-123-1, MKP2_2161_1, and 8M-all; and
f) Group 6: 8M-1, 8M-7, 1.2-3s or a Siphoviridae that is capable of infecting at least two of Klebsiella pneumoniae strains: KP2, CT-123-1, MKP2_2161_1, MKP2_251_B, and 8M-all, wherein the composition is capable of lysing each of Klebsiella pneumoniae strain KP2, and at least four Klebsiella pneumoniae strains selected from CT-141-1, CT-123-1, MKP2_2161_1, MKP2_251_B, MKP2_251_C and 8M-all.
2. The method of claim 1 , wherein the pharmaceutical composition is capable of lysing each of Klebsiella pneumoniae strains: KP2, CT-141-1, CT-123-1, MKP2_2161 1, MKP2_251_B, MKP2_251_C and 8M-all.
3. The method of claim 1 , wherein the pharmaceutical composition comprises bacteriophages MCoc5c and 8M-7 and lytic bacteriophages selected from at least one of Groups 1-3 and 5.
4. The method of claim 3 , wherein the pharmaceutical composition additionally comprises at least one bacteriophage selected from the group consisting of 1.2-3b, 1.2-2, and 1.2-3s.
5. The method of claim 4 , wherein the pharmaceutical composition additionally comprises at least one bacteriophage selected from KP2-5-1 and PKP-55.
6. The method of claim 1 , wherein the pharmaceutical composition comprises bacteriophages 1.2-3b, 1.2-2, and 1.2-3s.
7. The method of claim 6 , wherein the pharmaceutical composition additionally comprises bacteriophage Mcoc-5c.
8. The method of claim 1 , wherein the pharmaceutical composition is formulated for oral or rectal dosing.
9. The method of claim 1 , wherein the lytic bacteriophages are selected from at least four of the Groups 1-6.
10. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis.
11. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease.
12. The method of claim 1 , wherein the subject is infected with Klebsiella strain KP2.
13. The method of claim 1 , wherein the subject is infected with a mutant KP2.