Genes identified as required for proliferation in escherichia coli

Abstract

The sequences of nucleic acids encoding proteins required for E. coli proliferation are disclosed. The nucleic acids can be used to express proteins or portions thereof, to obtain antibodies capable of specifically binding to the expressed proteins, and to use those expressed proteins as a screen to isolate candidate molecules for rational drug discovery programs. The nucleic acids can also be used to screen for homologous genes that are required for proliferation in microorganisms other than E. coli. The nucleic acids can also be used to design expression vectors and secretion vectors. The nucleic acids of the present invention can also be used in various assay systems to screen for proliferation required genes in other organisms as well as to screen for antimicrobial agents.

What is claimed is:  
     
         1 . A method of inhibiting cellular proliferation comprising inhibiting the activity or reducing the amount of a polypeptide comprising a sequence selected from the group consisting of SEQ ID NOs. 243-357 and SEQ ID NOs. 359-398 or inhibiting the activity or reducing the amount of a nucleic acid encoding said polypeptide.  
     
     
         2 . The method of  claim 1 , wherein the cell in which proliferation is inhibited is selected from the group consisting of  Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter cloacae, Helicobacter pylori, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae, Salmonella typhimurium, Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Klebsiella pneumoniae, Salmonella typhi, Salmonella paratyphi, Salmonella cholerasuis, Staphylococcus epidermidis, Mycobacterium tuberculosis, Mycobacterium leprae, Treponema pallidum, Bacillus anthracis, Yersinia pestis, Clostridium botulinum, Campylobacter jejuni, Chlamydia trachomatus, Chlamydia pneumoniae  or any species falling within the genera of any of the above species.  
     
     
         3 . The method of  claim 1 , wherein the cell in which proliferation is inhibited is  Escherichia coli.    
     
     
         4 . A method for inhibiting cellular proliferation comprising introducing a compound which inhibits the activity or reduces the amount of a polypeptide comprising a sequence selected from the group consisting of SEQ ID NOs. 243-357 and SEQ ID NOs. 359-398 or which inhibits the activity or reduces the amount of a nucleic acid comprising a nucleotide sequence encoding said polypeptide into a cell.  
     
     
         5 . The method of  claim 4 , wherein said compound is an antisense nucleic acid.  
     
     
         6 . The method of  claim 5 , wherein said compound is an antisense nucleic acid comprising a sequence selected from the group consisting of SEQ ID NOs.: 405-485, or a proliferation-inhibiting portion thereof.  
     
     
         7 . The method of  claim 6 , wherein said proliferation inhibiting portion of one of SEQ ID NOs. 405-485 is a fragment comprising at least 10, at least 20, at least 25, at least 30, at least 50 or more than 50 consecutive nucleotides of one of SEQ ID NOs: 405-485.  
     
     
         8 . The method of  claim 4 , wherein said compound is a triple helix oligonucleotide.  
     
     
         9 . The method of  claim 4 , wherein the cell in which proliferation is inhibited is selected from the group consisting of  Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter cloacae, Helicobacter pylori, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae, Salmonella typhimurium, Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Klebsiella pneumoniae, Salmonella typhi, Salmonella paratyphi, Salmonella cholerasuis, Staphylococcus epidermidis, Mycobacterium tuberculosis, Mycobacterium leprae, Treponema pallidum, Bacillus anthracis, Yersinia pestis, Clostridium botulinum, Campylobacter jejuni, Chlamydia trachomatus, Chlamydia pneumoniae  or any species falling within the genera of any of the above species.  
     
     
         10 . The method of  claim 4 , wherein the cell in which proliferation is inhibited is  Escherichia coli.    
     
     
         11 . A method for inhibiting cellular proliferation comprising introducing a compound with activity against a gene corresponding to one of SEQ ID NOs.: 82-242 or with activity against the product of said gene into a population of cells expressing a gene.  
     
     
         12 . The method of  claim 11 , wherein said compound is an antisense nucleic acid.  
     
     
         13 . The method of  claim 12 , wherein said compound is an antisense oligonucleotide comprising a sequence selected from the group consisting of SEQ ID NOs.: 405-485, or a proliferation-inhibiting portion thereof.  
     
     
         14 . The method of  claim 13 , wherein said proliferation inhibiting portion of one of SEQ ID NOs. 405-485 is a fragment comprising at least 10, at least 20, at least 25, at least 30, at least 50 or more than 50 consecutive nucleotides of one of SEQ ID NOs: 405-485.  
     
     
         15 . The method of  claim 11 , wherein said compound is a triple helix oligonucleotide.  
     
     
         16 . The method of  claim 11 , wherein the cell in which proliferation is inhibited is selected from the group consisting of  Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter cloacae, Helicobacter pylori, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae, Salmonella typhimurium, Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Klebsiella pneumoniae, Salmonella typhi, Salmonella paratyphi, Salmonella cholerasuis, Staphylococcus epidermidis, Mycobacterium tuberculosis, Mycobacterium leprae, Treponema pallidum, Bacillus anthracis, Yersinia pestis, Clostridium botulinum, Campylobacter jejuni, Chlamydia trachomatus, Chlamydia pneumoniae  or any species falling within the genera of any of the above species.  
     
     
         17 . The method of  claim 11 , wherein the cell in which proliferation is inhibited is  Escherichia coli.