New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564

Dorte Frees; Julie Hove Andersen; Lene Hemmingsen; Kerttu Koskenniemi; Kristoffer Torbjørn Bæk; Musemma Kedir Muhammed; Dereje Dadi Gudeta; Tuula A. Nyman; Antti Sukura; Pekka Varmanen; Kirsi Savijoki

doi:10.1021/pr200956s

New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564

Dorte Frees, Julie Hove Andersen, Lene Hemmingsen, Kerttu Koskenniemi, Kristoffer Torbjørn Bæk, Musemma Kedir Muhammed, Dereje Dadi Gudeta, Tuula A. Nyman, Antti Sukura, Pekka Varmanen, Kirsi Savijoki

39 Citations (Scopus)

Abstract

In Staphylococcus aureus, ClpP proteases were previously shown to be essential for virulence and stress tolerance in strains derived from NCTC8325. Because these strains exhibit a severely reduced activity of the alternative sigma factor, SigB, we here reassessed the role of ClpP in SigB-proficient clinical strains. To this end, clpP was deleted in strains COL, Newman, and SA564, and the strains were characterized phenotypically. The proteomic changes accomplished by the clpP deletion in the different strains were analyzed using the 2-D DIGE technique. The proteomic analyses revealed mostly conserved changes in the protein profiles of the ClpP-deficient strains. Among the strain-specific changes were the up-regulation of prophage proteins that coincided with an increased spontaneous release of prophages and the relatively poorer growth of the clpP mutants in some strain backgrounds. Interestingly, the effect of ClpP on the expression of selected virulence genes was strain-dependent despite the fact that the expression of the global virulence regulators RNAIII, mgrA, sarZ, sarR, and arlRS was similarly changed in all clpP mutants. ClpP affected the expression of sarS in a strain-dependent manner, and we propose that the differential expression of sarS is central to the strain-dependent effect of ClpP on the expression of virulence genes.

Original language	English
Journal	Journal of Proteome Research
Volume	11
Issue number	1
Pages (from-to)	95-108
Number of pages	14
ISSN	1535-3893
DOIs	https://doi.org/10.1021/pr200956s
Publication status	Published - 1 Jan 2012

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Frees, D., Andersen, J. H., Hemmingsen, L., Koskenniemi, K., Bæk, K. T., Muhammed, M. K., Gudeta, D. D., Nyman, T. A., Sukura, A., Varmanen, P., & Savijoki, K. (2012). New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564. Journal of Proteome Research, 11(1), 95-108. https://doi.org/10.1021/pr200956s

New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564. / Frees, Dorte; Andersen, Julie Hove; Hemmingsen, Lene et al.
In: Journal of Proteome Research, Vol. 11, No. 1, 01.01.2012, p. 95-108.

Research output: Contribution to journal › Journal article › Research › peer-review

Frees, D, Andersen, JH, Hemmingsen, L, Koskenniemi, K, Bæk, KT, Muhammed, MK, Gudeta, DD, Nyman, TA, Sukura, A, Varmanen, P & Savijoki, K 2012, 'New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564', Journal of Proteome Research, vol. 11, no. 1, pp. 95-108. https://doi.org/10.1021/pr200956s

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title = "New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564",

abstract = "In Staphylococcus aureus, ClpP proteases were previously shown to be essential for virulence and stress tolerance in strains derived from NCTC8325. Because these strains exhibit a severely reduced activity of the alternative sigma factor, SigB, we here reassessed the role of ClpP in SigB-proficient clinical strains. To this end, clpP was deleted in strains COL, Newman, and SA564, and the strains were characterized phenotypically. The proteomic changes accomplished by the clpP deletion in the different strains were analyzed using the 2-D DIGE technique. The proteomic analyses revealed mostly conserved changes in the protein profiles of the ClpP-deficient strains. Among the strain-specific changes were the up-regulation of prophage proteins that coincided with an increased spontaneous release of prophages and the relatively poorer growth of the clpP mutants in some strain backgrounds. Interestingly, the effect of ClpP on the expression of selected virulence genes was strain-dependent despite the fact that the expression of the global virulence regulators RNAIII, mgrA, sarZ, sarR, and arlRS was similarly changed in all clpP mutants. ClpP affected the expression of sarS in a strain-dependent manner, and we propose that the differential expression of sarS is central to the strain-dependent effect of ClpP on the expression of virulence genes.",

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AU - Frees, Dorte

AU - Andersen, Julie Hove

AU - Hemmingsen, Lene

AU - Koskenniemi, Kerttu

AU - Bæk, Kristoffer Torbjørn

AU - Muhammed, Musemma Kedir

AU - Gudeta, Dereje Dadi

AU - Nyman, Tuula A.

AU - Sukura, Antti

AU - Varmanen, Pekka

AU - Savijoki, Kirsi

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N2 - In Staphylococcus aureus, ClpP proteases were previously shown to be essential for virulence and stress tolerance in strains derived from NCTC8325. Because these strains exhibit a severely reduced activity of the alternative sigma factor, SigB, we here reassessed the role of ClpP in SigB-proficient clinical strains. To this end, clpP was deleted in strains COL, Newman, and SA564, and the strains were characterized phenotypically. The proteomic changes accomplished by the clpP deletion in the different strains were analyzed using the 2-D DIGE technique. The proteomic analyses revealed mostly conserved changes in the protein profiles of the ClpP-deficient strains. Among the strain-specific changes were the up-regulation of prophage proteins that coincided with an increased spontaneous release of prophages and the relatively poorer growth of the clpP mutants in some strain backgrounds. Interestingly, the effect of ClpP on the expression of selected virulence genes was strain-dependent despite the fact that the expression of the global virulence regulators RNAIII, mgrA, sarZ, sarR, and arlRS was similarly changed in all clpP mutants. ClpP affected the expression of sarS in a strain-dependent manner, and we propose that the differential expression of sarS is central to the strain-dependent effect of ClpP on the expression of virulence genes.

AB - In Staphylococcus aureus, ClpP proteases were previously shown to be essential for virulence and stress tolerance in strains derived from NCTC8325. Because these strains exhibit a severely reduced activity of the alternative sigma factor, SigB, we here reassessed the role of ClpP in SigB-proficient clinical strains. To this end, clpP was deleted in strains COL, Newman, and SA564, and the strains were characterized phenotypically. The proteomic changes accomplished by the clpP deletion in the different strains were analyzed using the 2-D DIGE technique. The proteomic analyses revealed mostly conserved changes in the protein profiles of the ClpP-deficient strains. Among the strain-specific changes were the up-regulation of prophage proteins that coincided with an increased spontaneous release of prophages and the relatively poorer growth of the clpP mutants in some strain backgrounds. Interestingly, the effect of ClpP on the expression of selected virulence genes was strain-dependent despite the fact that the expression of the global virulence regulators RNAIII, mgrA, sarZ, sarR, and arlRS was similarly changed in all clpP mutants. ClpP affected the expression of sarS in a strain-dependent manner, and we propose that the differential expression of sarS is central to the strain-dependent effect of ClpP on the expression of virulence genes.

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New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564

Abstract

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