<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Single and multiple resistance to antibacterial drugs currently in use is spreading,
since they act against only a very small number of molecular targets; finding novel
targets for anti-infectives is therefore of great importance. All protein sequences from
three pathogens (<italic>Staphylococcus aureus, Mycobacterium tuberculosis</italic> and 
<italic>Escherichia coli</italic> O157:H7 EDL993) were assessed via comparative genomics methods for their
suitability as antibacterial targets according to a number of criteria, including the
essentiality of the protein, its level of sequence conservation, and its distribution in
pathogens, bacteria and eukaryotes (especially humans). Each protein was scored and
ranked based on weighted variants of these criteria in order to prioritize proteins as
potential novel broad-spectrum targets for antibacterial drugs. A number of proteins
proved to score highly in all three species and were robust to variations in the scoring
system used. Sensitivity analysis indicated the quantitative contribution of each metric
to the overall score. After further analysis of these targets, tRNA methyltransferase
(trmD) and translation initiation factor IF-1 (infA) emerged as potential and novel
antimicrobial targets very worthy of further investigation. The scoring strategy used
might be of value in other areas of post-genomic drug discovery.</p>
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Comp Funct Genomics. 2004 Jun; 5(4):304-327