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3 Fig. 3.7 Proteomic signatures of B. subtilis of different physiological stress/starved conditions. Comparisons ofthe protein profile of both exponentially growing and stressed B. subtilis cells reveal signature-like changes that are specific to certain stress stimuli (e.g., induction ofthe catalase KatA by oxidative stress). The individual sections ofthe 2-D gels display typical parts of the proteomic signatures of oxidative or heat stress, the stringent response or limitation of glucose or phosphate. (This figure also appears with the color plates.)

opening great chances to bring new and urgently required antibacterial drugs on the market (see Refs. [22-24] for review).

The postgenomic era of S. aureus began in 2001 with the publication ofthe genome sequence of two reference strains [25]. The S. aureus genome codes for about 2600-2700 proteins, among them about 1000 genes coding for proteins with still unknown functions. The genome sequence allowed the prediction of more than 60 gene regulators with helix-turn-helix motifs (among them are five SarA and three Fur homologues), 17 two-component systems, and two alternative r factors [25]. The complete genome sequence of seven and partial sequence information of another two S. aureus strains are now available in the databases. Preliminary genome data show that the various strains encode a different set of virulence factors or superantigens mostly located on pathogenicity islands or plasmids, which may be the reason for the broad spectrum of infectious caused by the different strains. The KEGG (www.genome.jp/kegg/pathway/map/) database has provided the first, still preliminary information on metabolic pathways encoded in the genome of S. aureus, from the carbon core catabolism including fermentation to the amino acid metabolism and other pathways.

The genome sequence information is required for functional genomic approaches; this is valid not only for DNA chip technologies, but also for high-throughput protein identification via mass spectrometry techniques. Proteomics can now be used to bring the genome sequence to the cell physiology of S. aureus, relying on the panorama view of proteomics providing an increasingly complete picture of the cell physiology of growing and nongrowing cells, including a comprehensive and new understanding of its pathogenicity. There is a great deal of information in the published literature about the regulation, structure, and function of various virulence factors, but only limited information about basic cellular physiology. It has become increasingly accepted that this basic cell physiology determines not only growth and survival, but pathogenicity as well. For this reason, much more knowledge about cell physiology is required to understand patho-genicity, which is probably a central point for the better and more successful combating of multiresistant strains and, thus, of various kinds of diseases. Functional genomics opens up the opportunity for a new and comprehensive understanding ofthe cell physiology and infection biology ofthe parasite.

56 | 3 Physiological Proteomics of Bacillus subtilis and Staphylococcus aureus ... 3.3.2

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