In vivo assay for identification of antimicrobial agents
AssigneesTrustees of Tufts College, President and Fellows of Harvard College
InventorsDebabrata RayChaudhuri, Marc Kirschner
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Abstract
The present invention provides novel in vivo assay systems and methods of using these assays systems to identify compounds that affect microbial cell division. The present invention further provides pharmaceutical compositions that have anti-microbial activity and methods of treating microbial infections.
Claims39
A method for identifying compounds that affect cell division comprising steps of:
- providing a bacterial strain expressing a mutant ftsZ protein under permissive conditions, wherein the bacterial strain is more sensitive to an inhibitor of cell division under permissive conditions than an isogenic wild type strain;
- contacting cells of the bacterial strain with a compound;
- and detecting a defect in cell division.
A method for identifying compounds that affect cell division, comprising steps of:
- providing a strain of bacteria that expresses a reduced amount of FtsZ compared to a wild-type strain;
- contacting the bacteria with a compound;
- and detecting a defect in cell division.
A method of identifying compounds that affect bacterial cell division, comprising steps of:
- contacting a cell that is defective in cell division under non-permissive conditions with a compound of interest;
- and detecting an alteration in the phenotype of the cell.
An assay system for identifying compounds that effect cell division, the assay system comprising a bacterial cell comprising a mutation affecting a multidrug efflux pump, wherein the bacterial cell further comprises a mutant FtsZ protein.
A method for identifying compounds that affect cell division, comprising steps of:
- providing a bacterial strain expressing a mutant ftsZ protein under permissive conditions;
- contacting cells of the bacterial strain with a compound;
- and detecting a defect in cell division, wherein the step of detecting comprises detecting an inhibitor of cell division by detecting a decrease in cell division or detecting bacteria that are longer and more filamentous than wild-type cells.
A method for identifying compounds that affect cell division, comprising steps of:
- providing a bacterial strain expressing mutant ftsZ protein under permissive conditions;
- contacting cells of the bacterial strain with a compound;
- and detecting a defect in cell division, wherein the bacterial strain is of a bacterial species selected from the group consisting of E. coli, V. cholerae, aureus, and S. flexneri.
A method of screening for compounds that affect cell division comprising steps of:
- providing a bacterial strain expressing a mutant ftsZ protein under permissive conditions;
- contacting cells of the bacterial strain with a compound not previously known to be an inhibitor of cell division;
- and detecting a defect in cell division.
A method for identifying compounds that affect cell division comprising steps of:
- providing a temperature-sensitive bacterial strain expressing a mutant ftsZ protein under permissive conditions;
- contacting cells of the bacterial strain with a compound;
- and detecting a defect in cell division.
A method for identifying compounds that affect cell division comprising steps of:
- providing a bacterial strain expressing a mutant ftsZ protein under permissive conditions;
- contacting cells of the bacterial strain with members of a compound library;
- and detecting a defect in cell division in cells contacted with a member of the library.
Dependencies are inferred from the claim text.