Karen Shaw;Robert Haselbeck;Vickie Brown-Driver;Kedar GC;John M. Finn;Mark Hilgers;Mark Stidham
发明人:
Vickie Brown-Driver,Kedar GC,John M. Finn,Robert Haselbeck,Mark Hilgers,Karen Shaw,Mark Stidham
申请号：
US13102856
公开号：
US08298543B2
申请日:
2011.05.06
申请国别(地区):
US
年份:
2012
代理人:
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 β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, 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.
