This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seggewiß, J.
Right arrow Articles by von Eiff, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seggewiß, J.
Right arrow Articles by von Eiff, C.

 Previous Article  |  Next Article 

Journal of Bacteriology, November 2006, p. 7765-7777, Vol. 188, No. 22
0021-9193/06/$08.00+0     doi:10.1128/JB.00774-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Reporter Metabolite Analysis of Transcriptional Profiles of a Staphylococcus aureus Strain with Normal Phenotype and Its Isogenic hemB Mutant Displaying the Small-Colony-Variant Phenotype{triangledown} ,{dagger}

Jochen Seggewiß,1 Karsten Becker,1 Oliver Kotte,2 Martin Eisenacher,3 Mohammad Reza Khoschkhoi Yazdi,1 Andreas Fischer,1 Peter McNamara,4 Nahed Al Laham,1 Richard Proctor,4 Georg Peters,1 Matthias Heinemann,2 and Christof von Eiff1*

Institute of Medical Microbiology, University of Münster, Münster, Germany,1 Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland,2 Integrated Functional Genomics (IFG), Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany,3 Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin4

Received 30 May 2006/ Accepted 24 August 2006

In this study, full-genome DNA microarrays based on the sequence of Staphylococcus aureus N315 were used to compare the transcriptome of a clinical S. aureus strain with a normal phenotype to that of its isogenic mutant with a stable small-colony-variant (SCV) phenotype (hemB::ermB). In addition to standard statistical analyses, systems biology advances were applied to identify reporter metabolites and to achieve a more detailed survey of genome-wide expression differences between the hemB mutant and its parental strain. Genes of enzymes involved in glycolytic and fermentative pathways were found to be up-regulated in the hemB mutant. Furthermore, our analyses allowed identification of additional differences between the normal-phenotype S. aureus and the SCV, most of which were related to metabolism. Profound differences were identified especially in purine biosynthesis as well as in arginine and proline metabolism. Of particular interest, a hypothetical gene of the Crp/Fnr family (SA2424) that is part of the arginine-deiminase (AD) pathway, whose homologue in Streptococcus suis is assumed to be involved in intracellular persistence, showed significantly increased transcription in the hemB mutant. The hemB mutant potentially uses the up-regulated AD pathway to produce ATP or (through ammonia production) to counteract the acidic environment that prevails intracellularly. Moreover, genes involved in capsular polysaccharide and cell wall synthesis were found to be significantly up-regulated in the hemB mutant and therefore potentially responsible for the changed cell morphology of SCVs. In conclusion, the identified differences may be responsible for the SCV phenotype and its association with chronic and persistent infections.

* Corresponding author. Mailing address: Institute of Medical Microbiology, University Hospital of Münster, Domagkstr. 10, 48149 Münster, Germany. Phone: 49-251-83-55360. Fax: 49-251-83-55350. E-mail: eiffc{at}uni-muenster.de.

{triangledown} Published ahead of print on 15 September 2006.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, November 2006, p. 7765-7777, Vol. 188, No. 22
0021-9193/06/$08.00+0     doi:10.1128/JB.00774-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wu, M., von Eiff, C., Al Laham, N., Tsuji, B. T. (2009). Vancomycin and Daptomycin Pharmacodynamics Differ against a Site-Directed Staphylococcus epidermidis Mutant Displaying the Small-Colony-Variant Phenotype. Antimicrob. Agents Chemother. 53: 3992-3995 [Abstract] [Full Text]  
  • Balibar, C. J., Shen, X., Tao, J. (2009). The Mevalonate Pathway of Staphylococcus aureus. J. Bacteriol. 191: 851-861 [Abstract] [Full Text]  
  • Tuchscherr, L. P. N., Buzzola, F. R., Alvarez, L. P., Lee, J. C., Sordelli, D. O. (2008). Antibodies to Capsular Polysaccharide and Clumping Factor A Prevent Mastitis and the Emergence of Unencapsulated and Small-Colony Variants of Staphylococcus aureus in Mice. Infect. Immun. 76: 5738-5744 [Abstract] [Full Text]  
  • Lannergard, J., von Eiff, C., Sander, G., Cordes, T., Seggewiss, J., Peters, G., Proctor, R. A., Becker, K., Hughes, D. (2008). Identification of the Genetic Basis for Clinical Menadione-Auxotrophic Small-Colony Variant Isolates of Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 4017-4022 [Abstract] [Full Text]  
  • Kohler, C., von Eiff, C., Liebeke, M., McNamara, P. J., Lalk, M., Proctor, R. A., Hecker, M., Engelmann, S. (2008). A Defect in Menadione Biosynthesis Induces Global Changes in Gene Expression in Staphylococcus aureus. J. Bacteriol. 190: 6351-6364 [Abstract] [Full Text]  
  • Hochgrafe, F., Wolf, C., Fuchs, S., Liebeke, M., Lalk, M., Engelmann, S., Hecker, M. (2008). Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection in Bacillus subtilis and Staphylococcus aureus. J. Bacteriol. 190: 4997-5008 [Abstract] [Full Text]  
  • Tsuji, B. T., von Eiff, C., Kelchlin, P. A., Forrest, A., Smith, P. F. (2008). Attenuated Vancomycin Bactericidal Activity against Staphylococcus aureus hemB Mutants Expressing the Small-Colony-Variant Phenotype. Antimicrob. Agents Chemother. 52: 1533-1537 [Abstract] [Full Text]  
  • Chatterjee, I., Kriegeskorte, A., Fischer, A., Deiwick, S., Theimann, N., Proctor, R. A., Peters, G., Herrmann, M., Kahl, B. C. (2008). In Vivo Mutations of Thymidylate Synthase (Encoded by thyA) Are Responsible for Thymidine Dependency in Clinical Small-Colony Variants of Staphylococcus aureus. J. Bacteriol. 190: 834-842 [Abstract] [Full Text]  
  • Al Laham, N., Rohde, H., Sander, G., Fischer, A., Hussain, M., Heilmann, C., Mack, D., Proctor, R., Peters, G., Becker, K., von Eiff, C. (2007). Augmented Expression of Polysaccharide Intercellular Adhesin in a Defined Staphylococcus epidermidis Mutant with the Small-Colony-Variant Phenotype. J. Bacteriol. 189: 4494-4501 [Abstract] [Full Text]  
  • Fuchs, S., Pane-Farre, J., Kohler, C., Hecker, M., Engelmann, S. (2007). Anaerobic Gene Expression in Staphylococcus aureus. J. Bacteriol. 189: 4275-4289 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»