The dissimilatory nitrate/nitride reduction system in Staphylococcus aureus: its regulation and role in virulence

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We described for the first time the nreABC (nitrogen regulation) operon that encodes a new staphylococcal two component regulatory system. It controls dissimilatory nitrate/nitrite reduction in response to oxygen. NreB is a cytosolic protein with four Nterminal cysteine residues. In the absence of oxygen, autophosphorylation of the cytoplasmic O2-sensor NreB of S. carnosus can be observed. NreC serves as the phosphoryl group acceptor, and phospho-NreC activates the expression of the nir and nar operons and the narT gene. Since an S. carnosus ¿nreABC deletion mutant shows a general growth defect irrespective of the presence of nitrate or nitrite, nreABC seem not only to be involved in dissimilatory nitrate reduction. In the frame of a PhD thesis we plan to construct and characterize an nreA-deletion mutant to study the role of NreA in the regulation system, its potential interaction with NreB and/or NreC and binding to nitrate/nitrite, respectively. We will create a nreABC deletion mutant in S. aureus to analyze by comparative transcriptome analysis how many and which genes are controlled by this regulon. Moreover, we want to study the role of dissimilatory nitrate/nitrite reduction in virulence and infection. We plan to carry out comparative cell biological studies with wild type and corresponding mutant strains with respect to resistance to phagocytotic killing, sensitivity to reactive nitrogen molecules created during oxidative burst, or antimicrobial peptide susceptibility under different growth conditions. For the last part of the thesis the PhD student is invited to Prof. Landmann, University Basel, to carry out in vivo studies for virulence in a murine model of systemic infection.