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.
Claims20
A method of treating a bacterial infection comprising a bacteria, such as a gram-negative bacteria, such as an A. baumannii or P. aeruginosa bacteria, comprising a mutation in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species 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;
- 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.
A method of treating a bacterial infection in a subject in need thereof, comprising 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 or salt thereof does not comprise a polymyxin peptide,
- wherein the formulation reduces a level of bacteria that comprises a mutation in the pmrABC operon gene, relative to a wildtype pmrABC operon gene present in a wild type A. baumannii ATCC 17978 or P. aeruginosa PA14 bacteria strain, to an extent comparable to a reduction by the formulation of a level of a bacteria strain with the wildtype pmrABC operon gene, as determined by an in vitro assay.
A method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject a formulation comprising an antimicrobial peptide or salt thereof, wherein:
- the administering is sufficient to treat the bacterial infection by inhibiting growth of bacteria with only a perturbation in a single gene, as determined by an in vitro assay;
- and
- after an extended exposure to said antimicrobial peptide, when the bacteria acquires a perturbation in at least two genes, the bacteria develop resistance against said antimicrobial peptide, wherein one of the at least two genes affects an outer membrane of the bacterial and one of the at least two genes affects aggregation of the bacteria.
Dependencies are inferred from the claim text.