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.
authors: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4 DK-1870, Frederiksberg C, Denmark.
authors: Dorte
authors: D
authors: Frees
authors: Julie Hove
authors: JH
authors: Andersen
authors: Lene
authors: L
authors: Hemmingsen
authors: Kerttu
authors: K
authors: Koskenniemi
authors: Kristoffer T
authors: KT
authors: Bæk
authors: Musemma Kedir
authors: MK
authors: Muhammed
authors: Dereje Dadi
authors: DD
authors: Gudeta
authors: Tuula A
authors: TA
authors: Nyman
authors: Antti
authors: A
authors: Sukura
authors: Pekka
authors: P
authors: Varmanen
authors: Kirsi
authors: K
authors: Savijoki
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049071:Endopeptidase Clp / Q000235:genetics*; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D010641:Phenotype; D039002:Prophages; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D057825:Two-Dimensional Difference Gel Electrophoresis; D014510:Urease / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020543:Proteome; C476149:SarS protein, Staphylococcus aureus; C112405:Sbi protein, Staphylococcus aureus; D015534:Trans-Activators; D037521:Virulence Factors; D049071:Endopeptidase Clp; D014510:Urease