摘要 |
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a ß-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GImU, GImU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
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申请人 |
RX3 PHARMACEUTICALS, INC.;DRIVER, VICKIE;FINN, JOHN, M.;GC, KEDAR;HASELBECK, ROBERT;HILGERS, MARK;STIDHAM, MARK;SHAW, KAREN |
发明人 |
DRIVER, VICKIE;FINN, JOHN, M.;GC, KEDAR;HASELBECK, ROBERT;HILGERS, MARK;STIDHAM, MARK;SHAW, KAREN |