Abstract: Complete genome sequences of several pathogenic bacteria have been
determined, and many more such projects are currently under way. While these
data potentially contain all the determinants of host-pathogen interactions and
possible drug targets, computational tools for selecting suitable candidates
for further experimental analyses are currently limited. Detection of bacterial
genes that are non-homologous to human genes, and are essential for the
survival of the pathogen represents a promising means of identifying novel drug
targets. We used a differential pathway analyses approach (based on KEGG data)
to identify essential genes from Pseudomonas aeruginosa. Our approach
identified 214 unique enzymes in P. aeruginosa that may be potential drug
targets and can be considered for rational drug design. About 40% of these
putative targets have been reported as essential by transposon mutagenesis data
elsewhere. Homology model for one of the proteins (LpxC) is presented as a case
study and can be explored for in silico docking with suitable inhibitors.
This approach is a step towards facilitating the search for new
antibiotics.
Keywords: Pseudomonas aeruginosa, Homo sapiens, comparative microbial genomics, KEGG, homology, MODELLER, LpxC, potential drug targets
