Genes identified as required for proliferation in Escherichia coli

A method of screening a candidate compound for the ability to inhibit proliferation of a microorganism said method comprising:

• (a) identifying a gene or gene product required for proliferation in a first microorganism;
• (b) identifying a homolog of said gene or gene product in a second microorganism;
• (c) identifying an inhibitory nucleic acid sequence which inhibits the activity of said homolog in said second microorganism;
• (d) contacting said second microorganism with a proliferation-inhibiting amount of said inhibitory nucleic acid, thus sensitizing said second microorganism,
• (e) contacting the sensitized microorganism of step (d) with a candidate compound;
• and
• (f) determining whether said candidate compound inhibits proliferation of said sensitized microorganism to a greater extent than said candidate compound inhibits proliferation of a nonsensitized microorganism.

A method of screening a candidate compound for the ability to inhibit proliferation said method comprising:

• (a) identifying an inhibitory nucleic acid sequence which inhibits the activity of a gene or gene product required for proliferation in a first microorganism;
• (b) contacting a second microorganism with a proliferation-inhibiting amount of said inhibitory nucleic acid, thus sensitizing said second microorganism;
• (c) contacting the proliferation-inhibited microorganism of step (b) with a candidate compound;
• and
• (d) determining whether said candidate compound inhibits proliferation of said sensitized second microorganism to a greater extent than said candidate compound inhibits proliferation of a nonsensitized second microorganism.

A method of screening a candidate compound for activity against a biological pathway required for proliferation, said method comprising:

• sensitizing a cell by expressing an antisense nucleic acid against a nucleic acid encoding a gene product required for proliferation in a cell to reduce the activity or amount of said gene product;
• contacting the sensitized cell with a candidate compound, wherein said candidate compound is not previously known to possess the ability to reduce proliferation;
• and
• determining whether said candidate compound inhibits the growth of said sensitized cell to a greater extent than said candidate compound inhibits the growth of an nonsensitized cell.

A method of screening a candidate compound for the ability to inhibit cellular proliferation, said method comprising:

• contacting a cell with an agent which reduces the activity or level of a gene product required for proliferation of said cell;
• contacting said cell with a candidate compound, wherein said candidate compound is not previously known to possess the ability to reduce cell proliferation;
• and
• determining whether said candidate compound reduces proliferation to a greater extent than said candidate compound reduces proliferation of a cell which has not been contacted with said agent.