Proteomic analyses of iron-responsive, Clp-dependent changes in Staphylococcus aureus.
Staphylococcus aureus is a frequent human pathogen that is capable of causing a wide range of life-threatening infections. A promising antibacterial target is the Clp proteolytic system, which performs the vital function of maintaining protein turnover within the cell. This system primarily impacts the bacterial response to various stresses by degrading specific proteins but can also regulate a number of physiological processes through protein degradation. A critical stress to which S. aureus must adapt during infection of a vertebrate host is nutrient iron limitation. We have previously shown that the Clp system impacts expression of genes required for heme-iron acquisition during iron limitation and is required for staphylococcal infection. Based on these data, we sought to further define the Clp-dependent impact on S. aureus during iron limitation by characterizing the proteomic profiles of mutants inactivated for components of the Clp protease, including ClpP, ClpC and ClpX, in high- and low-iron conditions. Our results reveal numerous proteins altered in abundance in the clp mutants and provide new insights into the staphylococcal proteolytic network during nutrient iron limitation.
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Allison J
AJ
Farrand
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
David B
DB
Friedman
Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
Michelle L
ML
Reniere
Faculty of Life Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
Hanne
H
Ingmer
Faculty of Life Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
Dorte
D
Frees
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA eric.skaar@vanderbilt.edu.
Eric P
EP
Skaar
D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D007501:Iron / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects*
D020543:Proteome; D007501:Iron; D049071:Endopeptidase Clp
2D-DIGE; degradation; protein