Phage therapy for alcohol-associated hepatitis

Abstract

Provided herein are therapeutic agents and compositions for the treatment of infections associated with alcohol-associated hepatitis. Also provided herein are methods for extending the host range of Enterococcus faecalis (E. faecalis) phages for treatment of alcohol-associated hepatitis related infections.

Description

Abstract This article provides therapeutic agents and compositions for treating infections associated with alcohol-related hepatitis. It also provides methods for expanding the host range of Enterococcus faecalis phage to treat alcohol-related hepatitis-associated infections.

Claims

WHAT IS CLAIMED IS:

1. A method to evolve Entercoccus faecalis (E. faecalis) phage comprising infecting one or more E. faecalis strains with one or more parental phage and determining whether one or more evolved phage are produced.

2. The method of claim 1 wherein, the E. faecalis is cytolysin-positive.

3. The method of claim 1, wherein the host range of the E. faecalis includes the one or more phage.

4. The method of claim 1, wherein the host range of the E. faecalis does not include the one or more phage.

5. The method of claim 1, wherein at least one of the strains is susceptible to infection by the parental phage.

6. The method of claim 1, wherein at least one of the strains is not susceptible to infection by the parental phage.

7. Isolated phage produced by the method of claim 1 that can infect multiple E. faecalis strains, thereby having a wider host range than the one or more parental phage.

8. Isolated phage produced by the method of claim 1 that can infect parental phage resistant E. faecalis strains.

9. An isolated infecWLRXV^SKDJH^FRPSULVLQJ^6(4^,'^12^ 2 or a nucleotide sequence with at least 80%, 82%, 84% 85%, 86%, 88%, 90%, 92%, 94% 95%, 96%, 97%, 98% or 99% nucleic acid sequence identity thereto.

10. A composition comprising one or more of the isolated phage of claim 7 or a combination(s) thereof.

11. A method to treat a disease or condition comprising administering an effective amount of the composition of claim 10 to mammal in need thereof, wherein the disease or condition is alcoholic hepatitis, nonalcoholic steatohepatitis (NASH), liver cirrhosis and / or liver failure.

12. The method of claim 11, wherein the mammal is a human.

13. The method of claim 11, wherein the composition comprises a Myoviridae, Podoviridae, Spounaviridae or Siphoviridae phage, or any combination thereof.

14. The method of claim 11, wherein the phage is isolated from the mammal, and optionally amplified, prior to administration.

15. The method of claim 11, wherein the phage has broad host specificity and / or is a genetically modified phage.

16. The method of claim 11, wherein levels of Enterococcus cytolysin or cytolytic E. faecalis are monitored after administration of the composition.

17. The method of claim 11, wherein a cocktail of lytic phages is administered.

18. The method of claim 11, wherein the composition is orally administered.

19. The method of claim 11, wherein the composition is a tablet.

20. The method of claim 11, wherein the composition is a sustained release dosage form.

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