Method for re-sensitizing vancomycin resistant bacteria which selectively cleave a cell wall depsipeptide
AssigneesThe Trustees of Columbia University in the City of New York, The Rockefeller University
InventorsGabriela Chiosis, Ivo G. Boneca, W. Clark Still
Life of this patent
Estimating the term…
Abstract
The present invention relates a method for re-sensitizing vancomycin resistant Gram-positive bacteria in which resistance results from the conversion of an amide bond to an ester bond in the cell wall peptide precursors of the bacteria which comprises using an antibacterial amount of vancomycin or a homolog of vancomycin and an amount of an agent effective to selectively cleave the ester bond so as to thereby re-sensitize vancomycin resistant bacteria.
Claims82
A method of treating a subject afflicted with an infection caused by vancomycin resistant Gram-positive bacteria in which resistance results from the conversion of an amide bond to an ester bond in the cell wall peptide precursors of the bacteria which comprises administering to the subject an antibacterial amount of vancomycin or a homolog of vancomycin and an amount of an agent effective to selectively cleave said ester bond so as to thereby treat the subject.
A method of killing vancomycin resistant Van A, Van B, Van D, or Van G Gram-positive bacteria which comprises contacting the bacteria with an agent that selectively cleaves D-Ala-D-Lac cell wall depsipeptides in the bacteria in an amount effective to cleave such depsipeptides and an antibacterial amount of vancomycin or a homolog of vancomycin so as to thereby kill the bacteria.
A method for determining whether a test compound selectively cleaves an ester bond present between two amino acid-like moieties in a depsipeptide which comprises contacting a compound comprising the structure X-Y, wherein each of X and Y are amino acid-like moieties and — is an ester bond with the test compound and determining whether the test compound cleaves the ester bond.
A method of treating a subject afflicted with an infection caused by glycopeptide antibiotic resistant Gram-positive bacteria in which resistance results from the conversion of an amide bond to an ester bond in the cell wall peptide precursors of the bacteria which comprises administering to the subject an antibacterial amount of a glycopeptide antibiotic and an amount of an agent effective to selectively cleave said ester bond so as to thereby treat the subject.
A method of killing glycopeptide antibiotic resistant Gram-positive bacteria which comprises contacting the bacteria with an agent that selectively cleaves D-Ala-D-Lac cell wall depsipeptides in the bacteria in an amount effective to cleave such depsipeptides and an antibacterial amount of the glycopeptide antibiotic so as to thereby kill the bacteria.
Dependencies are inferred from the claim text.