Small colony variants of Staphylococcus aureus reveal distinct protein profiles
Abstract
Small‐colony variants (SCVs) of Staphylococcus aureus represent a slow‐growing subpopulation causing chronic and relapsing infections due to their physiological adaptation on an intracellular lifestyle. In this first proteomic study on physiological changes associated with a natural, clinically derived SCV, its proteomic profile was investigated in comparison to corresponding isogenic strains displaying normal (clinical wild‐type strain, complemented hemB mutant and spontaneous revertant of the clinical SCV) and SCV phenotypes (hemB mutant and gentamicin‐induced SCV). Applying an ultra‐high resolution chromatography and high mass accuracy MS E‐based label‐free relative and absolute protein quantification approach, the whole cytoplasmic proteome of this strain sextet was investigated in a growth phase‐controlled manner covering early‐exponential, late‐exponential and stationary phases. Of 1019 cytoplasmic proteins identified, 154 were found to be differently regulated between strains. All SCV phenotypes showed down‐regulation of the tricarboxylic acid (TCA) cycle‐related proteins and of a protein cluster involved in purine/pyrimidine and folate metabolism. In contrast to hemB mutant and gentamicin‐induced SCVs, the clinically derived SCVs showed no prominent up‐regulation of glycolytic proteins. The spontaneous switch into the normal phenotype resulted in up‐regulation of TCA cycle‐related parts, while oxidative stress‐related proteins were down‐regulated. However, the natural revertant from the clinical SCV retained also dominant protein features of the clinical SCV phenotype. In conclusion, physiological changes between normal and SCV S. aureus phenotypes are more complex than reflected by defined electron transport chain‐interrupting mutants and their complemented counterparts.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Clinical and in vitro selected heme-auxotrophic SCVs have reduced catalase compared with corresponding wild-type bacteria.
“proteomics analysis of clinical and in vitro selected heme-auxotrophic SCVS revealed reduced catalase than in corresponding wild-type bacteria (74).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H <sub>2</sub> O <sub>2</sub> -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [74]
Cites
Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P. A., Murray, B. E., Persing, D. H., & Swaminathan, B. (1995) · Journal of Clinical Microbiology · doi:10.1128/jcm.33.9.2233-2239.1995 · Cited by 8,203 · see citing works
Staphylococcus aureus Infections
Lowy, F. D. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808203390806 · Cited by 6,018 · see citing works
Nasal Carriage as a Source of<i>Staphylococcus aureus</i>Bacteremia
von Eiff, C., Becker, K., Machka, K., Stammer, H., & Peters, G. (2001) · New England Journal of Medicine · doi:10.1056/nejm200101043440102 · Cited by 1,984 · see citing works
Self-citationQuantitative mass spectrometry in proteomics: a critical review
Bantscheff, M., Schirle, M., Sweetman, G. M. A., Rick, J. M., & Küster, B. (2007) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-007-1486-6 · Cited by 1,659 · see citing works
Absolute Quantification of Proteins by LCMSE
Silva, J. C., Gorenstein, M. V., Li, G.-Z., Vissers, J. P. C., & Geromanos, S. J. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500230-mcp200 · Cited by 1,529 · see citing works
Proctor, R. A., von Eiff, C., Kahl, B. C., Becker, K., McNamara, P., Herrmann, M., & Peters, G. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1384 · Cited by 1,175 · see citing works
Self-citationQuantitative Proteomic Analysis by Accurate Mass Retention Time Pairs
Silva, J. C., Denny, R., Dorschel, C. A., Gorenstein, M., Kass, I. J., Li, G., McKenna, T., Nold, M. J., Richardson, K., Young, P., et al. (2005) · Analytical Chemistry · doi:10.1021/ac048455k · Cited by 641 · see citing works
The development of the DIGE system: 2D fluorescence difference gel analysis technology
Marouga, R., David, S., & Hawkins, E. (2005) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-005-3126-3 · Cited by 641 · see citing works
Iron and Hydrogen Peroxide Detoxification Properties of DNA-binding Protein from Starved Cells
Zhao, G., Ceci, P., Ilari, A., Giangiacomo, L., Laue, T. M., Chiancone, E., & Chasteen, N. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202094200 · Cited by 417 · see citing works
Herbert, S., Ziebandt, A., Ohlsen, K., Schäfer, T., Hecker, M., Albrecht, D., Novick, R. P., & Götz, F. (2010) · Infection and Immunity · doi:10.1128/iai.00088-10 · Cited by 388 · see citing works
Horsburgh, M. J., Clements, M. O., Crossley, H., Ingham, E., & Foster, S. J. (2001) · Infection and Immunity · doi:10.1128/iai.69.6.3744-3754.2001 · Cited by 365 · see citing works
Anaerobic Gene Expression in Staphylococcus aureus
Fuchs, S., Pané‐Farré, J., Köhler, C., Hecker, M., & Engelmann, S. (2007) · Journal of Bacteriology · doi:10.1128/jb.00081-07 · Cited by 326 · see citing works
Quantification in Proteomics through Stable Isotope Coding: A Review
Julka, S., & Regnier, F. E. (2004) · Journal of Proteome Research · doi:10.1021/pr0340734 · Cited by 320 · see citing works
Horsburgh, M. J., Ingham, E., & Foster, S. J. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.2.468-475.2001 · Cited by 316 · see citing works
von Eiff, C., Heilmann, C., Proctor, R. A., Woltz, C., Peters, G., & Götz, F. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.15.4706-4712.1997 · Cited by 310 · cited 5× · see citing works
“complementation of the hemB defect in trans with the help of the vector pCE12 harbouring the wild-type hemB gene under the control of a leaky xylose inducible promoter and the second antibiotic marker encoded on the plasmid [7].”
BackgroundMethodInfluentialRegulation of inducible peroxide stress responses
Mongkolsuk, S., & Helmann, J. D. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03015.x · Cited by 293 · see citing works
Tuchscherr, L., Heitmann, V., Hussain, M., Viemann, D., Roth, J., von Eiff, C., Peters, G., Becker, K., & Löffler, B. (2010) · The Journal of Infectious Diseases · doi:10.1086/656047 · Cited by 275 · see citing works
Self-citationvon Eiff, C., Bettin, D., Proctor, R. A., Rolauffs, B., Lindner, N. J., Winkelmann, W., & Peters, G. (1997) · Clinical Infectious Diseases · doi:10.1086/516962 · Cited by 249 · see citing works
Self-citationShakil, S., Khan, R., Zarrilli, R., & Khan, A. U. (2007) · Journal of Biomedical Science · doi:10.1007/s11373-007-9194-y · Cited by 230 · see citing works
Gao, W., Chua, K., Davies, J. K., Newton, H. J., Seemann, T., Harrison, P. F., Holmes, N. E., Rhee, H., Hong, J., Hartland, E. L., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000944 · Cited by 218 · see citing works
Köck, R., Harlizius, J., Bressan, N., Laerberg, R., Wieler, L. H., Witte, W., Deurenberg, R. H., Voss, A., Becker, K., & Friedrich, A. W. (2009) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-009-0795-4 · Cited by 206 · see citing works
Self-citationvon Eiff, C., Becker, K., Metze, D., Lubritz, G., Hockmann, J., Schwarz, T., & Peters, G. (2001) · Clinical Infectious Diseases · doi:10.1086/320519 · Cited by 191 · see citing works
Self-citationClements, M. O., Watson, S. P., & Foster, S. J. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.13.3898-3903.1999 · Cited by 185 · see citing works
Acid-shock responses in Staphylococcus aureus investigated by global gene expression analysis
Bore, E., Langsrud, S., Langsrud, Ø., et al. (2007) · Microbiology · doi:10.1099/mic.0.2007/005942-0 · Cited by 172 · see citing works
Becher, D., Hempel, K., Sievers, S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008176 · Cited by 171 · see citing works
Ziebandt, A., Kusch, H., Degner, M., Jaglitz, S., Sibbald, M. J. J. B., Arends, J. P., Chlebowicz, M. A., Albrecht, D., Pantůček, R., Doškař, J., et al. (2010) · PROTEOMICS · doi:10.1002/pmic.200900313 · Cited by 158 · see citing works
Global Transcriptome Analysis of<i>Staphylococcus aureus</i>Response to Hydrogen Peroxide
Chang, W., Small, D. A., Toghrol, F., & Bentley, W. E. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.4.1648-1659.2006 · Cited by 152 · see citing works
Somerville, G. A., Saïd‐Salim, B., Wickman, J. M., Raffel, S. J., Kreiswirth, B. N., & Musser, J. M. (2003) · Infection and Immunity · doi:10.1128/iai.71.8.4724-4732.2003 · Cited by 142 · see citing works
Variant subpopulations of Staphylococcus aureus as cause of persistent and recurrent infections.
Proctor, R. A., Balwit, J. M., & Vesga, Ó. (1994) · PubMed · Cited by 139 · see citing works
Self-citationKöhler, C., von Eiff, C., Peters, G., Proctor, R. A., Hecker, M., & Engelmann, S. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.23.6928-6937.2003 · Cited by 133 · see citing works
Self-citationScherl, A., François, P., Charbonnier, Y., Deshusses, J., Koessler, T., Huyghe, A., Bento, M., Stahl-Zeng, J., Fischer, A., Masselot, A., et al. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-296 · Cited by 130 · see citing works
Lan, L., Cheng, A. G., Dunman, P. M., Missiakas, D. M., & He, C. (2010) · Journal of Bacteriology · doi:10.1128/jb.00928-09 · Cited by 130 · see citing works
von Eiff, C., McNamara, P. J., Becker, K., Bates, D. M., Lei, X.-H., Ziman, M., Bochner, B. R., Peters, G., & Proctor, R. A. (2005) · Journal of Bacteriology · doi:10.1128/jb.188.2.687-693.2006 · Cited by 129 · see citing works
Self-citationChatterjee, I., Kriegeskorte, A., Fischer, A., Deiwick, S., Theimann, N., Proctor, R. A., Peters, G., Herrmann, M., & Kahl, B. C. (2007) · Journal of Bacteriology · doi:10.1128/jb.00912-07 · Cited by 126 · see citing works
Self-citationSaini, A. K., Mapolelo, D. T., Chahal, H. K., Johnson, M. K., & Outten, F. W. (2010) · Biochemistry · doi:10.1021/bi1011546 · Cited by 125 · see citing works
Abu-Qatouseh, L., Chinni, S. V., Seggewiß, J., Proctor, R. A., Brosius, J., Rozhdestvensky, T. S., Peters, G., von Eiff, C., & Becker, K. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0597-2 · Cited by 119 · see citing works
Self-citationWolf, C., Hochgräfe, F., Kusch, H., Albrecht, D., Hecker, M., & Engelmann, S. (2008) · PROTEOMICS · doi:10.1002/pmic.200701062 · Cited by 115 · see citing works
Lannergård, J., von Eiff, C., Sander, G., Cordes, T., Seggewiβ, J., Peters, G., Proctor, R. A., Becker, K., & Hughes, D. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00668-08 · Cited by 108 · see citing works
Self-citationBates, D. M., Eiff, C. V., McNamara, P. J., Peters, G., Yeaman, M. R., Bayer, A. S., & Proctor, R. A. (2003) · The Journal of Infectious Diseases · doi:10.1086/374642 · Cited by 106 · see citing works
Self-citationProteomic profiling of cell envelope‐associated proteins from Staphylococcus aureus
Gatlin, C. L., Pieper, R., Huang, S., Mongodin, E. F., Gebregeorgis, E., Parmar, P. P., Clark, D. J., Alami, H., Papazisi, L., Fleischmann, R. D., et al. (2006) · PROTEOMICS · doi:10.1002/pmic.200500253 · Cited by 104 · see citing works
Besier, S., Ludwig, A., Ohlsen, K., Brade, V., & Wichelhaus, T. A. (2007) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2007.02.003 · Cited by 94 · see citing works
Rea, R. B., Hill, C., & Gahan, C. G. M. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8314-8322.2005 · Cited by 93 · see citing works
Köhler, C., Wolff, S., Albrecht, D., Fuchs, S., Becher, D., Büttner, K., Engelmann, S., & Hecker, M. (2005) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2005.08.002 · Cited by 87 · see citing works
Musher, D. M., BAUGHN, R. E., Templeton, G. B., & Minuth, J. N. (1977) · The Journal of Infectious Diseases · doi:10.1093/infdis/136.3.360 · Cited by 86 · see citing works
Seggewiß, J., Becker, K., Kotte, O., Eisenacher, M., Yazdi, M. R. K., Fischer, A., McNamara, P. J., Laham, N. A., Proctor, R. A., Peters, G., et al. (2006) · Journal of Bacteriology · doi:10.1128/jb.00774-06 · Cited by 83 · see citing works
Self-citationPieper, R., Bunai, C. L., Mongodin, E. F., Parmar, P. P., Huang, S., Clark, D. J., Fleischmann, R. D., Gill, S. R., & Peterson, S. N. (2006) · PROTEOMICS · doi:10.1002/pmic.200500764 · Cited by 78 · see citing works
Sifri, C. D., Baresch-Bernal, A., Calderwood, S. B., & von Eiff, C. (2006) · Infection and Immunity · doi:10.1128/iai.74.2.1091-1096.2006 · Cited by 74 · see citing works
Becker, K., Laham, N. A., Fegeler, W., Proctor, R. A., Peters, G., & von Eiff, C. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00847-06 · Cited by 72 · see citing works
Self-citationHecker, M., Reder, A., Fuchs, S., Pagels, M., & Engelmann, S. (2009) · Research in Microbiology · doi:10.1016/j.resmic.2009.03.008 · Cited by 61 · see citing works
A proteomic view of cell physiology and virulence of Staphylococcus aureus
Hecker, M., Becher, D., Fuchs, S., & Engelmann, S. (2009) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2009.10.006 · Cited by 61 · see citing works
Schmidt, F., Scharf, S. S., Hildebrandt, P., Burian, M., Bernhardt, J., Dhople, V. M., Kalinka, J., Gutjahr, M., Hammer, E., & Völker, U. (2010) · PROTEOMICS · doi:10.1002/pmic.201000045 · Cited by 48 · see citing works
Wilson, S., & Sanders, C. C. (1976) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.10.3.519 · Cited by 40 · see citing works
σ B Activity in a Staphylococcus aureus hemB Mutant
Senn, M. M., Bischoff, M., von Eiff, C., & Berger‐Bächi, B. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.21.7397-7406.2005 · Cited by 39 · see citing works
Small-colony Variants (SCVs) of Staphylococci: A Role in Foreign Body-associated Infections
von Eiff, C., & Becker, K. (2007) · The International Journal of Artificial Organs · doi:10.1177/039139880703000906 · Cited by 17 · see citing works
Self-citationFuchs, S., Mehlan, H., Kusch, H., Teumer, A., Zühlke, D., Berth, M., Wolf, C., Dandekar, T., Hecker, M., Engelmann, S., et al. (2010) · PROTEOMICS · doi:10.1002/pmic.200900388 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kahl, B. C., Becker, K., & Löffler, B. (2016) · Clinical Microbiology Reviews · doi:10.1128/cmr.00069-15 · Cited by 325 · see citing works
Self-citationGarcia, L. G., Lemaire, S., Kahl, B. C., Becker, K., Proctor, R. A., Denis, O., Tulkens, P. M., & Van Bambeke, F. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt072 · Cited by 177 · see citing works
Self-citationPainter, K. L., Strange, E., Parkhill, J., Bamford, K. B., Armstrong-James, D., & Edwards, A. M. (2015) · Infection and Immunity · doi:10.1128/iai.03016-14 · Cited by 153 · see citing works
Small colony variants (SCVs) of Staphylococcus aureus – A bacterial survival strategy
Kahl, B. C. (2014) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2013.05.016 · Cited by 118 · see citing works
Kriegeskorte, A., Block, D., Drescher, M., Windmüller, N., Mellmann, A., Baum, C., Neumann, C., Lorè, N. I., Bragonzi, A., Liebau, E., et al. (2014) · mBio · doi:10.1128/mbio.01447-14 · Cited by 89 · see citing works
Self-citationPhenotype Switching Is a Natural Consequence of Staphylococcus aureus Replication
Edwards, A. M. (2012) · Journal of Bacteriology · doi:10.1128/jb.00948-12 · Cited by 83 · see citing works
Discovery of an iron-regulated citrate synthase in Staphylococcus aureus
Cheung, J., Murphy, M. E. P., & Heinrichs, D. E. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.10.003 · Cited by 39 · see citing works
- Authors
- Kriegeskorte, A., König, S., Sander, G., Pirkl, A., Mahabir, E., Proctor, R. A., von Eiff, C., Peters, G., & Becker, K.
- Affiliations
- University Hospital Münster (DE)
- University of Münster (DE)
- University of Cologne (DE)
- University of Wisconsin–Madison (US)
- Corresponding author
- Becker, Karsten
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2011-05-18
- Volume
- 11
- Issue
- 12
- Pages
- 2476-2490
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- OpenAlex
- W2027622038
- Cited by
- 89
- References
- 55
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 9 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 11 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 6
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PROTEOMICS (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (BE2546/1-1)
- Bundesministerium für Bildung und Forschung (BMBF), Germany (01KI1009A)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- small colony variants, Staphylococcus aureus, TCA cycle, purine and pyrimidine metabolism, folate metabolism, spontaneous revertants, growth phase regulation, intracellular lifestyle, chronic infection, oxidative stress
- MeSH terms
- Bacterial Proteins, Chromatography, Citric Acid Cycle, Genotype, Gentamicins, Glycolysis, Heme, Mutation, Phenotype, Mass Spectrometry, Staphylococcal Infections, Staphylococcus aureus, Colony Count, Microbial, Gene Expression Regulation, Bacterial, Polymerase Chain Reaction, Genome, Bacterial, Gene Deletion, Gene Expression Profiling, Organisms, Genetically Modified, Proteomics, Genetic Association Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review