Methods and compositions for treatment of antibiotic-resistant bacterial infections
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsVaughn Cooper, Alfonso Santos López
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Abstract
Provided in this disclosure are methods of treating a bacterial infection comprising administering a formulation comprising an antimicrobial peptide described herein when administered to a subject. Further provided herein are methods of treating a bacterial infection wherein the bacterial infection comprises a bacterium with a mutation in a gene resulting in antibiotic resistance.
Claims18
A method of treating an infection caused by a bacteria selected from Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli, the bacteria comprising a mutation in a pmrB gene, a wspF gene, or a combination thereof, or a hypermutator bacteria strain of the bacteria, in a subject, comprising:
- obtaining a sample of the bacteria of the bacterial infection from the subject;
- administering to the subject a formulation comprising an antimicrobial peptide or salt thereof in a therapeutically effective amount to treat the bacterial infection, wherein the antimicrobial peptide comprises SEQ ID NO:
- 1;
- and
- monitoring a bacterial species obtained from the patient at one or more times after administration of the formulation for development of one or more additional mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species, wherein:
- one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO:
- 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, 408, and equivalent positions thereof, and/or
- one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO:
- 31, or an equivalent position thereof.
A method of treating an infection caused by Pseudomonas aeruginosa, the bacteria comprising a mutation in a pmrB gene, a wspF gene, an orfN gene, or a combination thereof, or a hypermutator bacteria strain of the bacteria, in a subject, comprising:
- obtaining a sample of the bacteria of the bacterial infection from the subject;
- administering to the subject a formulation comprising an antimicrobial peptide or salt thereof in a therapeutically effective amount to treat the bacterial infection, wherein the antimicrobial peptide comprises SEQ ID NO:
- 1;
- and
- monitoring a bacterial species obtained from the patient at one or more times after administration of the formulation for development of one or more additional mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species, wherein:
- one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO:
- 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, and 408,
- one or more of the mutations is in the orfN gene, wherein the orfN gene encodes a putative group 4 glycosyl transferase, wherein the at least one mutation in the orfN gene is in at least one codon of the orfN gene, and wherein the at least one mutation occurs in the putative group 4 glycosyl transferase at position 10 in SEQ ID NO:
- 30, and/or
- one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO:
- 31.
Dependencies are inferred from the claim text.