A Defect in Menadione Biosynthesis Induces Global Changes in Gene Expression in Staphylococcus aureus

Journal of Bacteriology - Tập 190 Số 19 - Trang 6351-6364 - 2008
Christian Köhler1, Christof von Eiff2, Manuel Liebeke3, Peter J. McNamara4, Michael Lalk3, Richard A. Proctor4,5, Michael Hecker1, Susanne Engelmann1
1Institut für Mikrobiologie, Universität Greifswald, Greifswald, Germany
2Institut für Medizinische Mikrobiologie, Universitätsklinikum Münster, Münster, Germany
3Institut für Pharmazeutische Biologie, Universität Greifswald, Greifswald, Germany
4Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
5Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Tóm tắt

ABSTRACT Both the high-resolution two-dimensional protein gel electrophoresis technique and full-genome DNA microarrays were used for identification of Staphylococcus aureus genes whose expression was changed by a mutation in menD . Because the electron transport chain is interrupted, the mutant should be unable to use oxygen and nitrate as terminal electron acceptors. Consistent with this, a mutation in menD was found to cause a gene expression pattern typically detected under anaerobic conditions in wild-type cells: proteins involved in glycolytic as well as in fermentation pathways were upregulated, whereas tricarboxylic acid (TCA) cycle enzymes were significantly downregulated. Moreover, the expression of genes encoding enzymes for nitrate respiration and the arginine deiminase pathway was strongly increased in the mutant strain. These results indicate that the menD mutant, just as the site-directed S. aureus hemB mutant, generates ATP from glucose or fructose mainly by substrate phosphorylation and might be defective in utilizing a variety of carbon sources, including TCA cycle intermediates and compounds that generate ATP only via electron transport phosphorylation. Of particular interest is that there are also differences in the gene expression patterns between hemB and menD mutants. While some anaerobically active enzymes were present in equal amounts in both strains (Ldh1, SACOL2535), other classically anaerobic enzymes seem to be present in higher amounts either in the hemB mutant (e.g., PflB, Ald1, IlvA1) or in the menD mutant ( arc operon). Only genes involved in nitrate respiration and the ald1 operon seem to be additionally regulated by a depletion of oxygen in the hemB and/or menD mutant.

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Tài liệu tham khảo

10.1128/JB.00609-06

Bates, D. M., C. von Eiff, P. J. McNamara, G. Peters, M. R. Yeaman, A. S. Bayer, and R. A. Proctor. 2003. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J. Infect. Dis. 187 : 1654-1661.

Baumert, N., C. von Eiff, F. Schaaff, G. Peters, R. A. Proctor, and H. G. Sahl. 2002. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb. Drug Resist. 8 : 253-260.

Bernhardt, J., J. Weibezahn, C. Scharf, and M. Hecker. 2003. Bacillus subtilis during feast and famine: visualization of the overall regulation of protein synthesis during glucose starvation by proteome analysis. Genome Res. 13 : 224-237.

Bochner, B. R., P. Gadzinski, and E. Panomitros. 2001. Phenotype microarrays for high-throughput phenotypic testing and assay of gene function. Genome Res. 11 : 1246-1255.

Brekasis, D., and M. S. Paget. 2003. A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2). EMBO J. 22 : 4856-4865.

Brouillette, E., A. Martinez, B. J. Boyll, N. E. Allen, and F. Malouin. 2004. Persistence of a Staphylococcus aureus small-colony variant under antibiotic pressure in vivo. FEMS Immunol. Med. Microbiol. 41 : 35-41.

Büttner, K., J. Bernhardt, C. Scharf, R. Schmid, U. Mäder, C. Eymann, H. Antelmann, A. Völker, U. Völker, and M. Hecker. 2001. A comprehensive two-dimensional map of cytosolic proteins of Bacillus subtilis. Electrophoresis 22 : 2908-2935.

Candiano, G., M. Bruschi, L. Musante, L. Santucci, G. M. Ghiggeri, B. Carnemolla, P. Orecchia, L. Zardi, and P. G. Righetti. 2004. Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis 25 : 1327-1333.

Doan, T., and S. Aymerich. 2003. Regulation of the central glycolytic genes in Bacillus subtilis: binding of the repressor CggR to its single DNA target sequence is modulated by fructose-1,6-bisphosphate. Mol. Microbiol. 47 : 1709-1721.

10.1128/JB.183.24.7341-7353.2001

10.1128/JB.01092-07

Eymann, C., A. Dreisbach, D. Albrecht, J. Bernhardt, D. Becher, S. Gentner, T. Tam Le, K. Büttner, G. Buurman, C. Scharf, S. Venz, U. Völker, and M. Hecker. 2004. A comprehensive proteome map of growing Bacillus subtilis cells. Proteomics 4 : 2849-2876.

10.1128/JB.184.9.2500-2520.2002

10.1128/JB.184.23.6624-6634.2002

Fillinger, S., S. Boschi-Muller, S. Azza, E. Dervyn, G. Branlant, and S. Aymerich. 2000. Two glyceraldehyde-3-phosphate dehydrogenases with opposite physiological roles in a nonphotosynthetic bacterium. J. Biol. Chem. 275 : 14031-14037.

10.1128/JB.00081-07

Georgellis, D., O. Kwon, and E. C. Lin. 2001. Quinones as the redox signal for the arc two-component system of bacteria. Science 292 : 2314-2316.

10.1007/s004380051001

10.1128/JB.00601-06

Hecker, M., A. Richter, A. Schroeter, L. Wölfel, and F. Mach. 1987. Synthesis of heat shock proteins following amino acid or oxygen limitation in Bacillus subtilis relA+ and relA strains. Z. Naturforsch. 42 : 941-947.

10.1128/JB.01846-07

Kahl, B., M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G. Peters. 1998. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J. Infect. Dis. 177 : 1023-1029.

10.1128/IAI.73.7.4119-4126.2005

Kamps, A., S. Achebach, I. Fedtke, G. Unden, and F. Götz. 2004. Staphylococcal NreB: an O2-sensing histidine protein kinase with an O2-labile iron-sulphur cluster of the FNR type. Mol. Microbiol. 52 : 713-723.

Koburger, T., J. Weibezahn, J. Bernhardt, G. Homuth, and M. Hecker. 2005. Genome-wide mRNA profiling in glucose starved Bacillus subtilis cells. Mol. Genet. Genomics 274 : 1-12.

10.1128/JB.185.23.6928-6937.2003

Kohler, C., S. Wolff, D. Albrecht, S. Fuchs, D. Becher, K. Büttner, S. Engelmann, and M. Hecker. 2005. Proteome analyses of Staphylococcus aureus in growing and non-growing cells: a physiological approach. Int. J. Med. Microbiol. 295 : 547-565.

10.1056/NEJM199808203390806

Ludwig, H., G. Homuth, M. Schmalisch, F. M. Dyka, M. Hecker, and J. Stülke. 2001. Transcription of glycolytic genes and operons in Bacillus subtilis: evidence for the presence of multiple levels of control of the gapA operon. Mol. Microbiol. 41 : 409-422.

10.1128/JB.00592-07

Malpica, R., B. Franco, C. Rodriguez, O. Kwon, and D. Georgellis. 2004. Identification of a quinone-sensitive redox switch in the ArcB sensor kinase. Proc. Natl. Acad. Sci. USA 101 : 13318-13323.

Malpica, R., G. R. Sandoval, C. Rodriguez, B. Franco, and D. Georgellis. 2006. Signaling by the arc two-component system provides a link between the redox state of the quinone pool and gene expression. Antioxid. Redox Signal. 8 : 781-795.

10.1128/JB.01395-07

10.1128/jb.140.2.671-679.1979

Pragman, A. A., Y. Ji, and P. M. Schlievert. 2007. Repression of Staphylococcus aureus SrrAB using inducible antisense srrA alters growth and virulence factor transcript levels. Biochemistry 46 : 314-321.

Proctor, R. A., P. van Langevelde, M. Kristjansson, J. N. Maslow, and R. D. Arbeit. 1995. Persistent and relapsing infections associated with small-colony variants of Staphylococcus aureus. Clin. Infect. Dis. 20 : 95-102.

Proctor, R. A., C. von Eiff, B. C. Kahl, K. Becker, P. McNamara, M. Herrmann, and G. Peters. 2006. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat. Rev. Microbiol. 4 : 295-305.

Richardson, A. R., P. M. Dunman, and F. C. Fang. 2006. The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity. Mol. Microbiol. 61 : 927-939.

10.1128/jb.117.2.911-913.1974

Schröder, A., R. Kland, A. Peschel, C. von Eiff, and M. Aepfelbacher. 2006. Live cell imaging of phagosome maturation in Staphylococcus aureus infected human endothelial cells: small colony variants are able to survive in lysosomes. Med. Microbiol. Immunol. 195 : 185-194.

10.1128/JB.00774-06

Seifert, H., C. von Eiff, and G. Fatkenheuer. 1999. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient. Emerg. Infect. Dis. 5 : 450-453.

10.1128/iai.25.3.902-911.1979

10.1128/IAI.74.2.1091-1096.2006

Throup, J. P., F. Zappacosta, R. D. Lunsford, R. S. Annan, S. A. Carr, J. T. Lonsdale, A. P. Bryant, D. McDevitt, M. Rosenberg, and M. K. Burnham. 2001. The srhSR gene pair from Staphylococcus aureus: genomic and proteomic approaches to the identification and characterization of gene function. Biochemistry 40 : 10392-10401.

10.1128/IAI.70.10.5428-5437.2002

Viegas, F. B., M. Wattenberg, F. van Ham, J. Kriss, and M. McKeon. 2007. ManyEyes: a site for visualization at Internet scale. IEEE Trans. Vis. Comput. Graph. 13 : 1121-1128.

von Eiff, C., K. Becker, D. Metze, G. Lubritz, J. Hockmann, T. Schwarz, and G. Peters. 2001. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier's disease. Clin. Infect. Dis. 32 : 1643-1647.

von Eiff, C., D. Bettin, R. A. Proctor, B. Rolauffs, N. Lindner, W. Winkelmann, and G. Peters. 1997. Recovery of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis. Clin. Infect. Dis. 25 : 1250-1251.

10.1128/jb.179.15.4706-4712.1997

10.1128/JB.188.2.687-693.2006

Wendrich, T. M., and M. A. Marahiel. 1997. Cloning and characterization of a relA/spoT homologue from Bacillus subtilis. Mol. Microbiol. 26 : 65-79.

Ziebandt, A. K., D. Becher, K. Ohlsen, J. Hacker, M. Hecker, and S. Engelmann. 2004. The influence of agr and sigmaB in growth phase dependent regulation of virulence factors in Staphylococcus aureus. Proteomics 4 : 3034-3047.

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Journal of Bacteriology

Tập 190 Số 19

6351-6364

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