a Genes (i.e., so-called orthologous genes) are counted which occur in E. coli, P. aeruginosa, S. aureus, S. pneumoniae, S. pyogenes, and E.faecalis and which are described as being probably essential in at least two of the mentioned species. Where data for only one strain were available, the essentiality test results from B. subtilis were also considered. The species spectrum of a grampositive/gram-negative problem solver drug is mainly represented by the bacteria mentioned above plus E. faecium, ofwhich no complete genome data have been published yet. The species E. coli and P. aeruginosa do not need to be considered when focusing on a gram-positive-only spectrum. It is not yet known whether all ofthese genes are really essential in all ofthe listed organisms. Thus, the number oftarget structures will decrease. One example is the broadly conserved and essential methionyl-tRNA synthetase which is counted in this table (enzyme class: ligases), but which is nonessential in 40% of clinical isolates of S. pneumoniae (see text). Genome comparison for counting orthologous genes and enzyme classification were performed using the genome analysis software-database system Phyloso-pher (Genedata, Basel, Switzerland). b For definition of functional systems, complexes of two or more proteins carrying out one enzymatic function were counted as one entity. For instance, the ribosomal subunits were summarized as one functional system, or the four bacterial acetyl-CoA carboxylase subunits represent one enzymatic function. The definitions were made according to common knowledge deduced from the literature.

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