Antimicrobial therapy

Abstract

Methods and compositions comprising hogocidin peptides (SH-lantibiotics), derivatives and variants are provided. Also provided are methods and compositions comprising probiotic compositions utilizing strains of S. hominis and S. epidermidis that produce hogocidin, hogocidin-like peptides, or other inhibitors of skin pathogens. Methods of treatment for microbial skin infections and atopic dermatitis are also provided.

1 . A composition comprising a thickened topical formulation of one or more probiotic bacterial strains and optionally, a prebiotic compound, a protectant, humectant, emollient, abrasive, salt, and/or surfactant;
 wherein the one or more probiotic bacterial strain comprises one or more bacterial strains of the genus  Staphylococcus;      wherein the one or more probiotic bacterial strains produces a peptide having a sequence selected from the group consisting of SEQ ID NO: 2, 4, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, and 55 and any combination thereof and wherein such peptide is optionally post-translationally modified; and   wherein the composition is formulated for the topical treatment of disorders of dysbiosis of the skin, scalp, or mucosae.   
     
     
         2 . The composition according to  claim 1 , wherein the one or more probiotic bacterial strain comprises  Staphylococcus epidermidis, Staphylococcus hominis  or a combination of  Staphylococcus epidermidis  and  Staphylococcus hominis.    
     
     
         3 . The composition according to  claim 2 , wherein the one or more probiotic bacterial strain comprises  Staphylococcus epidermidis  strains MO34, MO38, A11, AMT1, AMT5-C5, and/or AMT5-G6. 
     
     
         4 . The composition according to  claim 2 , wherein one or more probiotic bacterial strains comprises  Staphylococcus hominis  strains A9, C2, AMT2, AMT3, AMT4-C2, AMT4-G1, and/or AMT4-D12. 
     
     
         5 . The composition according to  claim 2 , wherein each probiotic bacterial strain demonstrates a Fatty Acid Methyl Ester profile corresponding to one of those shown in any of  FIG. 11, 12, 13, 14, 15, 16, 17, 18 , or  19 . 
     
     
         6 . (canceled) 
     
     
         7 . The composition according to  claim 1 , wherein the one or more probiotic bacterial strains is provided in a live form. 
     
     
         8 . The composition according to  claim 1 , wherein the one or more probiotic bacterial strains is provided in a lyophilized or freeze-dried or spray dried form. 
     
     
         9 . The composition according to  claim 8 , wherein the probiotic bacterium can be reconstituted into a live form. 
     
     
         10 . A method of treating skin or mucosal infections, atopic dermatitis, psoriasis, mastitis, acne, or other disorders related to skin dysbiosis in humans or other mammals by applying to the skin or mucosa an effective amount of the composition of  claim 1  to a subject in need thereof. 
     
     
         11 . The method according to  claim 10 , wherein the composition is applied topically. 
     
     
         12 . The method according to  claim 10 , wherein the composition is formulated as a cream, ointment, unguent, spray, powder, oil, thickened formulation or poultice. 
     
     
         13 . A composition comprising one or more of a hogocidin peptide, derivative or variant, an SH-lantibiotic peptide, an SH-antimicrobial, an SE-lantibiotic peptide, and/or an SE antimicrobial;
 wherein the hogocidin peptide comprise a sequence that is at least 95% identical to SEQ ID NO:2 or 4, or a biologically active fragment thereof having antimicrobial activity; and   wherein the composition further comprises one or more thickeners, solvents, emulsifiers, or pharmaceutically acceptable carriers or excipients.   
     
     
         14 . The composition according to  claim 13 , further comprising a cathelicidin peptide, derivative or variant. 
     
     
         15 . The composition according to  claim 13 , wherein the peptide comprises one or more D-amino acids or non-naturally occurring amino acids. 
     
     
         16 . A composition according to  claim 13 , wherein the hogocidin peptide, SH-lantibiotic peptide, SH-antimicrobial, SE-lantibiotic peptide, or SE antimicrobial is produced in situ by one or more of  Staphylococcus hominis  strain A9,  Staphylococcus hominis  strain C2,  Staphylococcus hominis  strain AMT2,  Staphylococcus hominis  strain AMT3,  Staphylococcus hominis  strain AMT4-C2,  Staphylococcus hominis  strain AMT4-G1,  Staphylococcus hominis  strain AMT4-D12,  Staphylococcus epidermidis  strain AMT1,  Staphylococcus epidermidis  strain SE-A11 , Staphylococcus epidermidis  strain AMT5-C5,  Staphylococcus epidermidis  strain AMT5-G6 and  Staphylococcus epidermidis  strain M034. 
     
     
         17 . A composition according to  claim 13 , wherein the peptide is formulated for topical administration. 
     
     
         18 . A composition according to  claim 17 , wherein the formulation comprises a lotion, ointment cream, powder, unguent, oil, or spray. 
     
     
         19 . A composition according to  claim 13 , wherein the hogocidin peptide, derivative or variant comprises a sequence selected from SEQ ID NO:2 or SEQ ID NO:4. 
     
     
         20 . The composition according to  claim 13 , wherein the one or more of a hogocidin peptide, derivative or variant, an SH-lantibiotic peptide, an SH-antimicrobial, an SE-lantibiotic peptide, an SE antimicrobial, and a cathelicidin peptide, derivative or variant is provided as an extract or lysate of  Staphylococcus hominis  strain A9,  Staphylococcus hominis  strain C2,  Staphylococcus hominis  strain AMT2,  Staphylococcus hominis  strain AMT3,  Staphylococcus hominis  strain AMT4-C2,  Staphylococcus hominis  strain AMT4-G1,  Staphylococcus hominis  strain AMT4-D12,  Staphylococcus epidermidis  strain AMT1,  Staphylococcus epidermidis  strain SE-A11,  Staphylococcus epidermidis  strain AMT5-C5,  Staphylococcus epidermidis  strain AMT5-G6 and  Staphylococcus epidermidis  strain MO34. 
     
     
         21 . A method for treating skin or mucosal infection or atopic dermatitis in a subject comprising contacting the subject with an effective amount of a composition of  claim 13 . 
     
     
         22 . The method according to  claim 21 , wherein the contacting is by topical administration or optionally by contacting the subject with one or more of SH-lantibiotic or bacteriocin-producing  Staphylococcus hominis  strains A9, C2, AMT2, AMT3, AMT4-C2, AMT4-G1, AMT4-D12 and  Staphylococcus epidermidis  strains AMT5-G6 and MO34. 
     
     
         23 . A recombinant vector comprising a polynucleotide encoding a polypeptide that is at least 95% identical to SEQ ID NO:2 or 4, or a biologically active fragment thereof having antimicrobial activity. 
     
     
         24 . The recombinant vector of  claim 23 , wherein the vector comprises a polynucleotide that encodes a polypeptide of SEQ ID NO:2 or 4. 
     
     
         25 . The recombinant vector of  claim 23 , wherein the vector comprises a polynucleotides that encodes a polypeptide of SEQ ID NO:2 from about amino acid 32 to about amino acid 61. 
     
     
         26 . The recombinant vector of  claim 23 , wherein the vector comprises a polynucleotide that encodes a polypeptide of SEQ ID NO:4 from about amino acid 29 to about amino acid 66. 
     
     
         27 . The recombinant vector of  claim 23 , wherein the vector comprises a polynucleotide that is at least 95% identical to SEQ ID NO:1 or 3 and encodes a polypeptide of SEQ ID NO:2 or 4, respectively. 
     
     
         28 . (canceled) 
     
     
         29 . A host cell engineered to express a recombinant vector of  claim 23 . 
     
     
         30 . The host cell of  claim 29 , wherein the host cell is a non-pathogenic attenuated host cell. 
     
     
         31 . A recombinant polypeptide produced by the host cell of  claim 29 . 
     
     
         32 . A composition comprising the host cell of  claim 29 . 
     
     
         33 . A composition comprising the host cell of  claim 30 . 
     
     
         34 . (canceled)