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Fig. 3.11 Sectors of 2-D gels covering the region where the Gap protein is located. Protein extracts of S. aureus COL before (control) and 5 min after addition of 100 mM H2O2 were separated on 2-D gels. Note the shift of Gap to a more acidic position (Gapox) under oxidative stress conditions. Both spots (Gapred and Gapox) were analyzed by tandem hybrid mass spectrometry. A modified peptide was found in Gapox. The sequencing of this peptide indicated the oxidation of a cysteinyl residue (Cys-151) to sulfonic acid.

Oxacillin as a cell-wall-active antibiotic induced a proteomic signature that indicated oxidative damage and protein stress [32]. However, the data are still preliminary and do not allow a complete picture as yet. Triton X-100 as another surface-active substance induced members of the rB and SarA regulons [26]. It is interesting to note that strains sensitive and those resistant to methicillin showed a slightly different proteomic signature in response to Triton X-100 [26].

Proteomic starvation signatures are not yet available, probably because of the difficulty of designing growth media that trigger a well-defined stationary phase caused by phosphate, glucose, or nitrogen starvation. Stationary phase cells showed significant de-repression of the TCA cycle enzymes and repression of the glycolytic enzymes compared to cells grown on glucose excess. Because S. aureus has the ability to invade different tissues, oxygen could be one of the most crucial growth-limiting stimuli forcing adaptational processes against oxygen limitation and starvation. S. aureus can grow under low-oxygen conditions by fermentation or nitrate respiration. A two-component system, SrrAB, which has a strong similarity to the ResDE two-component system of B. subtilis [33], is probably the main global regulator of the aerobic-anaerobic shift of metabolism. Throup et al. [34] provided the first proteomic data indicating that SrrAB (SrhSR) controls the upre-gulation of fermentation enzymes (lactate dehydrogenase, alcohol dehydrogenase) as well as the downregulation of aerobic TCA cycle enzymes (succinyl-CoA synthetase, aconitase, fumarase). A mutant in srrAB is characterized by a severe growth defect under anaerobic conditions [34].

There are only a few proteomic data available on general stress/starvation responses (see Refs. [10, 35] for review). The rB-dependent response seems to be totally different from the general stress response of B. subtilis, in relation not only to the signal transduction pathway of environmental stimuli to rB, but also the genes controlled by rB [36, 37] (Pane-Farre et al., submitted). Recent data suggest that the rB regulon does not belong to the heat stress stimulon and only a minority of genes are involved in the development of a nonspecific multiple stress resistance, the main feature of the general stress response in Bacillus species. Proteo-mic data in combination with more complete transcriptomic data allowed this surprising conclusion [36, 37] (Pane-Farre et al., submitted). These transcriptomic results support recent data that rB-dependent proteins in S. aureus are directly involved in the virulence in a catheter infection model (Lorenz et al., submitted). Proteomic information on other general stress or starvation responses such as the RelA-dependent stringent control or the probably related CodY regulon is still lacking.

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