Compositions comprising propionibacterium acnes bacteriophages for treating acne

Abstract

Provided herein are, inter alia, compositions, systems, and methods for preventing or treating acne. Included are compositions, combinations, systems, and methods comprising at least one Propionibacterium acnes bacteriophage, at least one anti-acne compound, and a pharmaceutically acceptable carrier. Also included are compositions, combinations, and systems comprising a Propionibacterium acnes bacteriophage and an enzyme. Methods for preventing or treating acne are also provided.

What is claimed is: 
     
         1 . A composition comprising at least one  Propionibacterium acnes  bacteriophage, at least one anti-acne compound, and a pharmaceutically acceptable carrier. 
     
     
         2 . The composition of  claim 1 , which does not comprise a probiotic bacterium. 
     
     
         3 . The composition of  claim 1 , wherein the composition further comprises a  P. acnes  biofilm degrading enzyme. 
     
     
         4 . The composition of  claim 1 , wherein the at least one anti-acne compound is salicylic acid. 
     
     
         5 . The composition of  claim 4 , wherein the salicylic acid is present at a concentration of 0.5% to 2% (weight/volume). 
     
     
         6 . The composition of  claim 5 , wherein the salicylic acid is present at a concentration of less than 0.5% but greater than about 0.1% (weight/volume). 
     
     
         7 . The composition of  claim 1 , wherein the at least one anti-acne compound is sulfur. 
     
     
         8 . The composition of  claim 7 , wherein the sulfur is present at a concentration of 3% to 10% (weight/volume). 
     
     
         9 . The composition of  claim 7 , wherein the sulfur is present at a concentration of less than 3% but greater than about 0.1%, 0.5%, 1%, 1.5%, 2%, or 2.5% (weight/volume). 
     
     
         10 . The composition of  claim 1 , wherein the at least one anti-acne compound is resorcinol and sulfur. 
     
     
         11 . The composition of  claim 10 , wherein the resorcinol is present at a concentration of 2% and sulfur is present at a concentration of 3% to 8% (weight/volume). 
     
     
         12 . The composition of  claim 1 , wherein the at least one anti-acne compound comprises resorcinol monoacetate and sulfur. 
     
     
         13 . The composition of  claim 12 , wherein the resorcinol monoacetate is present at a concentration of 3% and sulfur is present at a concentration of 3% to 8% (weight/volume). 
     
     
         14 . The composition of  claim 1 , wherein the anti-acne compound is an antibiotic, a retinoid, or an alpha-hydroxy acid. 
     
     
         15 . The composition of  claim 1 , wherein the  Propionibacterium acnes  bacteriophage is a naturally occurring  Propionibacterium acnes  bacteriophage. 
     
     
         16 . The composition of  claim 1 , wherein the  P. acnes  bacteriophage is a lytic  P. acnes  bacteriophage. 
     
     
         17 . The composition of  claim 1 , wherein the  P. acnes  bacteriophage comprises a linear double stranded DNA genome. 
     
     
         18 . The composition of  claim 1 , wherein the  P. acnes  bacteriophage is within the bacteriophage family Siphoviridae. 
     
     
         19 . The composition of  claim 1 , wherein the genome of the  P. acnes  bacteriophage comprises a nucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 1. 
     
     
         20 . The composition of  claim 3 , wherein the enzyme is a  P. acnes  biofilm degrading enzyme. 
     
     
         21 . The composition of  claim 20 , wherein the enzyme is a glycosidase, a protease, a DNAse, or a restriction endonuclease. 
     
     
         22 . The composition of  claim 20 , wherein the enzyme is a glycosidase. 
     
     
         23 . The composition of  claim 22 , wherein the glycosidase is a glycoside hydrolase. 
     
     
         24 . The composition of  claim 23 , wherein the enzyme catalyzes the hydrolysis of linear polymers of N-acetyl-D-glucosamines. 
     
     
         25 . The composition of  claim 24 , wherein the enzyme is a β-hexosaminidase. 
     
     
         26 . The composition of  claim 25 , wherein the enzyme is hydrolyzes β-1,6-glycosidic linkages of acetylglucosamine polymers. 
     
     
         27 . The composition of  claim 20 , wherein the enzyme is a DNAse I, a restriction endonuclease, papain, bromelain, Trypsin, Proteinase K, Subtilisin, serratiopeptidase, dispersin, alginate lyase, amylase, or cellulase. 
     
     
         28 . The composition of  claim 20 , wherein the enzyme is Dispersin B. 
     
     
         29 . The composition of  claim 20 , wherein the enzyme is a protease, and the protease is proteinase K or subtilisin. 
     
     
         30 . The composition of  claim 1 , further comprising an anti-aging enzyme. 
     
     
         31 . The composition of  claim 30 , wherein the anti-aging enzyme is a superoxide dismutase or a peroxidase. 
     
     
         32 . The composition of  claim 1 , further comprising a probiotic bacterium. 
     
     
         33 . The composition of  claim 32 , wherein the probiotic bacterium is a probiotic a  P . sp.,  Staphylococcus  sp., and/or  Corynebacterium  sp. bacterium. 
     
     
         34 . The composition of  claim 32 , wherein the probiotic bacterium is a bacterium within the class Betaproteobacteria. 
     
     
         35 . The composition of  claim 33 , wherein the probiotic bacterium is a probiotic  P. acnes  bacterium. 
     
     
         36 . The composition of  claim 35 , wherein the  P. acnes  bacterium
 (a) comprises a 16S rDNA sequence with a T992C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (b) comprises a 16S rDNA sequence with a T838C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (c) comprises a 16S rDNA sequence with a C1322T mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (d) comprises a 16S rDNA sequence with a C986T mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (e) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 3;   (f) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 4;   (g) does not comprise a linear plasmid;   (h) does not comprise a plasmid that comprises a virulence factor; and/or   (i) does not comprises a plasmid that encodes an extrachromosomal lipase and/or a tight adhesion virulence factor.   
     
     
         37 . The composition of  claim 35 , wherein the  P. acnes  bacterium:
 (a) produces less than about 20% of the level of lipase that is produced by a pathogenic  P. acnes  strain when grown in a planktonic culture;   (b) produces less than about 10% of the level of lipase that is produced by a pathogenic  P. acnes  strain when grown in an adherent culture;   (c) adheres to epithelial cells at least 50% less than a pathogenic  P. acnes  strain; and/or   (d) is less inflammatory than a pathogenic  P. acnes  strain.   
     
     
         38 . The composition of  claim 35 , further comprising at least one additional probiotic bacterium. 
     
     
         39 . The composition of  claim 38 , wherein said at least one additional probiotic bacterium comprises  Propionibacterium granulosum  and/or  Propionibacterium avidum.    
     
     
         40 . The composition of  claim 37 , wherein said pathogenic  P. acnes  strain
 (a) comprises a 16S rDNA sequence with a G1058C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (b) comprises a 16S rDNA sequence with a G1058C and an A1201C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (c) comprises a 16S rDNA sequence with a G529A mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (d) comprises a 16S rDNA sequence with a G1004A and a T1007C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (e) comprises a 16S rDNA sequence with a G1268A mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (f) comprises a 16S rDNA sequence with a T554C and a G1058C mutation compared to the KPA171202 type strain 16S rDNA sequence set forth as SEQ ID NO: 2;   (g) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 5;   (h) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 6;   (i) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 7;   (j) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 8;   (k) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 9; and/or   (l) comprises a 16S rDNA sequence that is identical to the sequence of SEQ ID NO: 10.   
     
     
         41 . The composition of  claim 1 , further comprising at least one additional  P. acnes  bacteriophage. 
     
     
         42 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier comprises an emulsion. 
     
     
         43 . The composition of  claim 42 , wherein the emulsion is an oil-in-water emulsion or a water-in-oil emulsion. 
     
     
         44 . The composition of  claim 1 , which is in the form of a cream, lotion, suspension, or aqueous solution. 
     
     
         45 . A combination comprising at least one  Propionibacterium acnes  bacteriophage and at least one anti-acne compound, wherein each of the at least one  Propionibacterium acnes  bacteriophage and the at least one anti-acne compound is in a composition that further comprises a pharmaceutically acceptable carrier. 
     
     
         46 . The combination of  claim 45 , wherein the at least one  P. acnes  bacteriophage and the at least one anti-acne compound are within separate compositions. 
     
     
         47 . The combination of  claim 46 , wherein the at least one anti-acne compound is benzoyl peroxide. 
     
     
         48 . The combination of  claim 47 , wherein the benzoyl peroxide is present at a concentration of 2.5% to 10% (weight/volume). 
     
     
         49 . The combination of  claim 47 , wherein the benzoyl peroxide is present at a concentration of less than 2.5% but greater than about 0.1%, 0.5%, 1%, 1.5%, or 2% (weight/volume). 
     
     
         50 . A method of treating acne in a subject in need thereof, the method comprising administering an effective amount of the composition of  claim 1  to the subject. 
     
     
         51 . The method of  claim 50 , wherein the composition is administered topically. 
     
     
         52 . A method of treating acne in a subject in need thereof, the method comprising administering an effective amount of the combination of  claim 45  to the subject. 
     
     
         53 . A composition comprising a  Propionibacterium acnes  bacteriophage and an enzyme. 
     
     
         54 . A combination comprising a  Propionibacterium acnes  bacteriophage and an enzyme. 
     
     
         55 . A composition consisting essentially of at least one  Propionibacterium acnes  bacteriophage, at least one anti-acne compound, and a pharmaceutically acceptable carrier.