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113 out of347 studied genes

a (Potentially) essential genes are defined as genes which could not be inactivated. Validation of essentiality using conditional expression systems will reduce the number of essential genes. Essentiality of genes has been studied in vitro in complex medium. Genes validated this way are considered to be probably indispensable in vivo, too. The best validated study has been performed in B subtilis, so that in this case the number of essential genes seems to be realistic.

a (Potentially) essential genes are defined as genes which could not be inactivated. Validation of essentiality using conditional expression systems will reduce the number of essential genes. Essentiality of genes has been studied in vitro in complex medium. Genes validated this way are considered to be probably indispensable in vivo, too. The best validated study has been performed in B subtilis, so that in this case the number of essential genes seems to be realistic.

Another way to identify novel targets is to look at the molecular mechanisms which bacteriophages apply in order to arrest critical cellular processes. By sequencing 26 S. aureus phages Liu et al. identified 31 novel polypeptide families that inhibited growth upon expression in S. aureus [61]. For one of these polypeptides, they found Dnal as the target by affinity chromatography. Dnal is an essential protein, which is a helicase loader required for primosome assembly during the initiation of DNA replication. Screening for small molecule inhibitors of the phage protein-Dnal interaction using a fluorescence polarization assay even enabled them to identify antibiotic compounds acting via the helicase loader. A phage genomics platform of this kind could be expanded to other species and could provide valuable information as well as screening tools for novel or unexplored targets.

Table 23.3 Number of potential targets for discovery of gram-positive/negative and gram-positive-only problem solver (subdivided into enzyme classes)

Gram-positive/ gram-negative Gram-positive only

Conserved essential proteins[a]

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