Antibiotic discovery: is it all in the genes?

Even discounting these exceptional cses, however, the prioritization of S. aureus and S. pneumoniae ORFs has proven to be very useful by eliminating hundreds of costly anti-infective 'dead-ends' while highlighting many targets that may have escaped the experienced researcher's intuition. To improve the historical description or evolutionary relationships of the proteins in the SB database, more sensitive tools are applied that incorporate more information inherent in each protein, such as conserved amino acid residues or conserved secondary and tertiary structural domains. Also, phylogenetic analyses are used to resolve evolutionary relationships among different species as well as to distinguish between levels of orthology and paralogy. However, these techniques are not yet automated and still rely heavily on the computational biologist's intuition. Molecular evolution and anti-infectives research seem to be an unlikely winning combination in today's competitive pharmaceutical environment. In practice, however, the application of molecular evolutionary principles has helped to direct experimental efforts towards molecular targets that are more likely to be sustainable in the drug development pipeline. In addition, the methods of evolutionary biology and comparative genomics will continue to play an important role in expanding our general knowledge about the biology of pathogenic bacteria.